Dichloroacetyl chloride → HCID 58728760, compound

HRID 1992172Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:8]2([CH2:21][CH2:22][N:23]3[C@H:28]4[CH2:29][CH2:30][C@@H:24]3[CH2:25][CH:26]([N:31]3[C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=5[N:33]=[C:32]3[CH3:40])[CH2:27]4)[CH2:13][CH2:12][N:11]([C:14](=[O:20])[C@@H:15]3[CH2:19][CH2:18][CH2:17][NH:16]3)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:41][CH:42]([Cl:46])[C:43](Cl)=[O:44].CCN(C(C)C)C(C)C>>[Cl:41][CH:42]([Cl:46])[C:43]([N:16]1[CH2:17][CH2:18][CH2:19][C@H:15]1[C:14]([N:11]1[CH2:12][CH2:13][C:8]([CH2:21][CH2:22][N:23]2[C@H:28]3[CH2:29][CH2:30][C@@H:24]2[CH2:25][CH:26]([N:31]2[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=4[N:33]=[C:32]2[CH3:40])[CH2:27]3)([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH2:9][CH2:10]1)=[O:20])=[O:44]

Participants

Reactant 3

HCID 6593Dichloroacetyl chloride

HCID 81531Diisopropylethylamine

HCID 68677313HCID 68677313, compound

Product 1

HCID 58728760HCID 58728760, compoundYield 49.2%

Procedure

1-((1R,5S)-8-{2-[1-[1-(dichloroacetyl)-L-prolyl]-4-(3-fluorophenyl)-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole was obtained from treating 1,1-dimethylethyl (2S)-2-[(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-pyrrolidinecarboxylate (0.645 g, 1.01 mmol) with HCl as outlined in the procedure for Example 890 to form 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)-1-L-prolyl-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (0.545 g, 99%). 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)-1-L-prolyl-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (0.050 g, 0.09 mmol), Dichloro-acetyl chloride (0.013 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, 1-((1R,5S)-8-{2-[1-[1-(dichloroacetyl)-L-prolyl]-4-(3-fluorophenyl)-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (0.029 g, 49%) as an oil. ES-LCMS m/z 654 (M+1).

Sources & evidence

ORD record: ord-9ae9b3f117ec4aacbb5e070e8a91b3b9
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07645771B2

Reaction notes

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