Chloroacetyl chloride → HCID 58728785, compound

HRID 1992182Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:8]2([CH2:22][CH2:23][N:24]3[C@H:29]4[CH2:30][CH2:31][C@@H:25]3[CH2:26][CH:27]([N:32]3[C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=5[N:34]=[C:33]3[CH3:41])[CH2:28]4)[CH2:13][CH2:12][N:11]([C:14](=[O:21])[C:15]([CH3:20])([NH2:19])[CH:16]([CH3:18])[CH3:17])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:42][CH2:43][C:44](Cl)=[O:45].CCN(C(C)C)C(C)C>>[Cl:42][CH2:43][C:44]([NH:19][C:15]([C:14]([N:11]1[CH2:12][CH2:13][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)([CH2:22][CH2:23][N:24]2[C@H:29]3[CH2:30][CH2:31][C@@H:25]2[CH2:26][CH:27]([N:32]2[C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=4[N:34]=[C:33]2[CH3:41])[CH2:28]3)[CH2:9][CH2:10]1)=[O:21])([CH3:20])[CH:16]([CH3:17])[CH3:18])=[O:45]

Participants

Reactant 3

HCID 6577Chloroacetyl chloride

HCID 81531Diisopropylethylamine

HCID 68679724HCID 68679724, compound

Product 1

HCID 58728785HCID 58728785, compoundYield 52.4%

Procedure

2-chloro-N-{1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-1,2-dimethylpropyl}acetamide was obtained from treating 1,1-dimethylethyl {1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-1,2-dimethylpropyl}carbamate, example 915, (0.623 g, 0.94 mmol) with HCl as outlined in the procedure for Example 890 to form 1-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)-2,3-dimethyl-1-oxo-2-butanamine (0.524 g, 99%). 1-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)-2,3-dimethyl-1-oxo-2-butanamine (0.050 g, 0.09 mmol), Chloro-acetyl chloride (0.011 g, 0.09 mmol) and DIEA (0.034 g, 0.534 mmol) were reacted following the procedure outlined in Example 890 to give the title compound, 2-chloro-N-{1-[(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-1,2-dimethylpropyl}acetamide (0.030 g, 52%) as an oil. ES-LCMS m/z 636 (M+1).

Sources & evidence

ORD record: ord-90fb35a87b024613bff93e0c4b83d4e1
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07645771B2

Reaction notes

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