Sodium Bicarbonate → 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-ylamino)bicyclo[3.1.0]hexan-3-ylcarbamate

HRID 56371

Reaction equation

HRID 56371 reaction equation
[NH2:1][C@H:2]1[C@@H:7]([NH:8][C:9](=[O:17])[O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][C@H:5]2[C@@H:3]1[CH2:4]2.Cl[C:19]1[N:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:29]3[C:34]([Cl:35])=[C:33]([O:36][CH3:37])[CH:32]=[C:31]([O:38][CH3:39])[C:30]=3[Cl:40])[CH:25]=2)[N:20]=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(OCC)(=O)C>[Cl:35][C:34]1[C:33]([O:36][CH3:37])=[CH:32][C:31]([O:38][CH3:39])=[C:30]([Cl:40])[C:29]=1[C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([NH:1][C@H:2]1[C@@H:7]([NH:8][C:9](=[O:17])[O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:16])[CH3:15])[CH2:6][C@H:5]3[C@@H:3]1[CH2:4]3)[N:28]=[CH:27]2

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 899217722-Chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolineHCID 1317369152-trimethylsilylethyl N-[(1S,2R,3S,5S)-2-amino-3-bicyclo[3.1.0]hexanyl]carbamate

Product 1

HCID 1317369142-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-ylamino)bicyclo[3.1.0]hexan-3-ylcarbamateYield 62.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-aminobicyclo[3.1.0]hexan-3-ylcarbamate (250 mg, 0.977 mmol), 2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline (300 mg, 0.814 mmol) and sodium bicarbonate (205 mg, 2.442 mmol) in N-methyl-2-pyrrolidone (10 mL) was stirred at 100° C. overnight. The reaction solution was cooled to room temperature, diluted with ethyl acetate (100 mL) and washed with water (eight times) and brine (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to afford a crude product, which was purified by silica gel column chromatography (ethyl acetate:petroleum ether=4:2) to afford the title compound (300 mg, 52%) as a yellow solid. MS (ES+) C28H34Cl2N4O4Si requires: 588, 590, found: 589, 591 [M+H]+.

Workup

  1. washwashed with water (eight times) and brine (50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford a crude product, which
  6. customwas purified by silica gel column chromatography (ethyl acetate:petroleum ether=4:2)

Sources & evidence

ORD record
ord-ea6964527a4d4262afbdc8f164fae667
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Linked notes

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