Chloroacetyl chloride → HCID 11455072, compound

HRID 1442986Notes

Reaction equation

HRID 1442986 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[Cl:6][C:7]1[CH:8]=[C:9]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:32][CH3:33])=[CH:22][C:23]=3[O:25][CH2:26][C@@H:27]3[CH2:31][CH2:30][CH2:29][NH:28]3)[N:18]=[CH:17][N:16]=2)[CH:10]=[CH:11][C:12]=1[F:13].C([N:37]([CH2:41][CH3:42])[CH:38]([CH3:40])C)(C)C.N1CCCC1>C(Cl)Cl>[Cl:6][C:7]1[CH:8]=[C:9]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:32][CH3:33])=[CH:22][C:23]=3[O:25][CH2:26][C@@H:27]3[CH2:31][CH2:30][CH2:29][N:28]3[C:3](=[O:4])[CH2:2][N:37]3[CH2:38][CH2:40][CH2:42][CH2:41]3)[N:18]=[CH:17][N:16]=2)[CH:10]=[CH:11][C:12]=1[F:13]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 68676425HCID 68676425, compound

Product 1

HCID 11455072HCID 11455072, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Chloroacetyl chloride (21 μl) was added in one portion to a stirred solution of N-(3-chloro-4-fluorophenyl)-7-methoxy-5-[(2S)-pyrrolidin-2-ylmethoxy]-quinazolin-4-amine (96 mg) (obtained as described in Example 1, preparation of starting materials) and N,N-diisopropylethylamine (83 μl) in DCM (3 ml) at room temperature. The reaction mixture was stirred for 40 minutes and then pyrrolidine (80 μl) was added in one portion and the reaction mixture was stirred for 15 hours 30 minutes under a nitrogen atmosphere. The reaction mixture was diluted with DCM (10 ml) and washed with saturated aqueous sodium hydrogen carbonate and water. The organic layer was dried (MgSO4) and concentrated in vacuo to leave a yellow oil, which was purified by column chromatography using 0-10% methanol in DCM as eluent to give the title compound as a white solid (75 mg, 61%); NMR Spectrum (DMSO-d6) 9.90 (s, 1H), 8.40 (s, 1H), 8.10 (dd, 1H), 7.72-7.62 (m, 1), 7.39 (t, 1H), 6.82 (d, 1H), 6.78 (d, 1H), 4.62-4.54 (m, 1H), 4.34 (dd, 1H), 4.16 (dd, 1H), 3.90 (s, 3H), 3.58-3.48 (m, 2H), 3.28-3.16 (m, 2H), 2.48 (br s, 4H), 2.10-1.82 (m, 4H), 1.6 (br s, 4H); Mass spectrum MH+ 514.

Workup

  1. stirringthe reaction mixture was stirred for 15 hours 30 minutes under a nitrogen atmosphere
  2. washwashed with saturated aqueous sodium hydrogen carbonate and water
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto leave a yellow oil, which
  6. customwas purified by column chromatography

Sources & evidence

ORD record
ord-e1263be0227343638acc57e52ff21846
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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