Phenyl chloroformate → HCID 58771923, compound

HRID 1175078Notes

Reaction equation

HRID 1175078 reaction equation
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[Cl:11][C:12]1[C:13]([F:38])=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:36][CH3:37])=[C:26]([O:29][CH:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1.C(N(C(C)C)CC)(C)C>ClCCl>[Cl:11][C:12]1[C:13]([F:38])=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:36][CH3:37])=[C:26]([O:29][CH:30]4[CH2:31][CH2:32][N:33]([C:2]([O:4][C:5]5[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=5)=[O:3])[CH2:34][CH2:35]4)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 15891Phenyl chloroformateHCID 81531DiisopropylethylamineHCID 10408840N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine

Product 1

HCID 58771923HCID 58771923, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Phenyl chloroformate (43 mg, 0.25 mmol) was added dropwise to a mixture of N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine (100 mg, 0.25 mmol) [prepared as described in Example 1] and diisopropylethylamine (50 μl, 0.30 mmol) in dichloromethane (2 ml). The mixture was stirred at room temperature for 18 hours. After evaporation of the solvents under vacuum, the residue was diluted in DMF (1 ml) and purified on an HPLC column (C18, 5 microns, 19 mm diameter, 100 mm length) of a preparative HPLC-MS system eluting with a mixture of water and acetonitrile containing 2 g/l of ammonium formate (gradient) to give the title compound as a solid (76 mg, 57%). NMR spectrum (DMSO-d6) 1.81 (m, 2H), 2.11 (m, 2H), 3.39 (m, 1H), 3.58 (m, 1H), 3.79 (m, 1H), 3.90 (m, 1H), 3.96 (s, 3H), 4.78 (m, 1H), 7.15 (d, 2H), 7.23 (m, 2H), 7.30 (m, 1H), 7.39 (m, 2H), 7.50 (m, 2H), 7.91 (s, 1H), 8.38 (s, 1H); Mass spectrum: MH+ 523.

Workup

  1. customAfter evaporation of the solvents under vacuum
  2. additionthe residue was diluted in DMF (1 ml)
  3. custompurified on an HPLC column (C18, 5 microns, 19 mm diameter, 100 mm length) of a preparative HPLC-MS system
  4. washeluting with a mixture of water and acetonitrile containing 2 g/l of ammonium formate (gradient)

Sources & evidence

ORD record
ord-86c2aec0e5c4497d86d2b8d39a2df32c
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

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