Chloroacetyl chloride → HCID 57794564, compound

HRID 2099377Notes

Reaction equation

HRID 2099377 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].Cl.Cl.[Cl:8][C:9]1[C:10]([F:35])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][C@H:29]4[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1.C(N(C(C)C)CC)(C)C.[CH3:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1>C(Cl)Cl>[Cl:8][C:9]1[C:10]([F:35])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][C@H:29]4[CH2:34][CH2:33][CH2:32][N:31]([C:3](=[O:4])[CH2:2][N:49]5[CH2:50][CH2:51][N:46]([CH3:45])[CH2:47][CH2:48]5)[CH2:30]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 68908613HCID 68908613, compound

Product 1

HCID 57794564HCID 57794564, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Chloroacetyl chloride (47 μl) was added to a solution of N-(3-chloro-2-fluorophenyl)-6-methoxy-7-[(3S)-piperidin-3-yloxy]quinazolin-4-amine dihydrochloride (250 mg) and diisopropylethylamine (373 μl) in methylene chloride (10 ml) and the mixture was stirred at ambient temperature for 1 hour. 1-Methylpiperazine (228 mg) was added, and the solution stirred for 1 hour before being washed with aqueous sodium hydroxide (2M, 10 ml) and water (10 ml). The organics were then purified by flash column chromatography eluting with methylene chloride/7N ammonia solution in methanol (97/3) to give a foam. This was re-precipitated by stirring in diethyl ether (20 ml) to give the title product as a white solid (0.135 g); 1H NMR Spectrum: (DMSO d6) 1.42-1.67 (m, 1H), 1.70-1.95 (m, 2H), 1.98-2.48 (m, 9H), 2.18 (s, 3H), 2.82-3.05 (m, 1H), 3.20-4.02 (m, 8H), 4.68 (m, 1H,), 7.30 (m, 1H), 7.34 (s, 1H), 7.44-7.60 (m, 2H), 7.82 (m, 1H), 8.38 (s, 1H), 9.64 (m, 1H); Mass Spectrum: (M+H)+ 543; melting point 120 to 121° C.

Workup

  1. stirringthe solution stirred for 1 hour
  2. washbefore being washed with aqueous sodium hydroxide (2M, 10 ml) and water (10 ml)
  3. customThe organics were then purified by flash column chromatography
  4. washeluting with methylene chloride/7N ammonia solution in methanol (97/3)
  5. customto give a foam
  6. customThis was re-precipitated
  7. stirringby stirring in diethyl ether (20 ml)

Sources & evidence

ORD record
ord-e474d81da0474e5aa2f65c8294895fd4
Source dataset
uspto-grants-2009_08
Patent number
US07569577B2

Reaction notes

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