* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 - 25℃; for 2.0h;Inert atmosphere;
Example 41. Preparation of compound S10: To a solution of acid S3 (45 mg, 0.11 mmol) in anhydrous DMF (1.5 mL) was added <strong>[1170108-38-9]tert-butyl azetidin-3-ylmethylcarbamate hydrochloride</strong> (53 mg, 0.14 mmol) followed by DIPEA (0.1 mL, 0.54 mmol). The reaction mixture was cooled to 0 C and HATU (48 mg, 0.216 mmol) was added. Upon complete addition, the reaction as warmed up to 25C and stirred for 2 h under N2. The reaction was then quenched with pH 7 buffer (phosphate, 10 mL) and extracted with EtOAc (3 x 15 mL). The combined organic extracts were washed with water (5 mL) and brine (5 mL), dried over Na2S04 and concentrated. The mixture was purified by silica flash column chromatography (DCM:MeOH = 1000: 1 to 100: 1) to afford title compound S10 (45 mg, 71%) as a yellow solid. LC-HRMS, m/z 607.1433 [M+Na]+; Calcd for C32H28N207SNa+ : 607.1617.
tert-butyl ((1-(2-aminopyridin-4-yl)azetidin-3-yl)methyl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96%
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 120℃; for 24.0h;Sealed tube;
For isopropyl alcohol / N, N-diisopropylethylamine (50mL / 25mL)4-chloropyridin-2-amine 8-1 (2.50 g, 19.5 mmol) solution inTert-butyl (azetidin-3-ylmethyl) carbamate hydrochloride 8-2 (5.60 g, 25.4 mmol) was added. The reaction mixture was heated in a sealed tube at 120 C for 24 hours.The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was distinguished between EtOAc and saturated sodium bicarbonate solution.The layers were separated; the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was washed with hexane to obtain((1- (2-aminopyridin-4-yl) azetidin-3-yl) methyl) t-butylaminoformate 8-3 (5.2 g, 96%),An off-white solid, which was used directly in the next step without further purification.
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 120℃; for 24.0h;Sealed tube;
To a solution of 4~chloropyridin~2 -amine 8-1 (2.50 g, 19.5 mrnol) in isopropanoyNN-diisopropylethylamine (50 mL/25 mL) was added /erf-butyl(azetidin-3- ylmethyl)carbamate hydrochloride 8-2 (5.60 g. 25.4 mmol). The reaction mixture was heated at 120 C in a sealed tube for 24 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between EtOAd and saturated sodium bicarbonate solution. The layers were separated; the organic layer was dried over sodium sulphate, filtered and concentrated . Hie residue was washed with hexanes to provide /en-butyl ((l -(2-aminopyridin-4-yl)azetidm-3- yl)methyl)carbamate 8-3 (5.2 g, 96%) as an off-white solid, which was used for next step without further purification. ESHAPCI-MS m/z 279 M - S i j .
tert-butyl ((1-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)azetidin-3-yl)methyl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
52%
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃; for 12.0h;
Step A: A solution of 2-chloro-5,6-dimethyl-1H-benzo[d]imidazole (135 mg, 0.75 mmol), t-Butyl(azetidin-3-yl)methyl-carbamate:HCl (333 mg, 1.50 mmol) and DIEA (0.33 mL, 1.9 mmol) in DMSO (1.5 mL) were stirred at 100 C. for 12 hrs. The reaction was diluted with EtOAc and water. The aqueous layer was separated and extracted with EtOAc (3×). The combined organics were washed with water, brine, dried over Na2SO4, concentrated and chromatographed on silica gel (24 g) eluting with a 0-to-5% MeOH/DCM (with 1% conc. NH4OH) gradient to give 128 mg (52%) of tert-butyl ((1-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)azetidin-3-yl)methyl)carbamate as a light tan solid. MS (ESI) (M+H+) m/z=331. LCMS Ret time (UV 215/254): 0.83 min.
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