Dichloromethane → HCID 178502396, compound

HRID 1411351Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:39])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[C:31]([F:33])[C:30]([NH2:34])=[CH:29][C:28]=3[C:35]([F:38])([F:37])[F:36])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C(Cl)Cl.CC(N(C)C)=O.[F:49][C:50]1[CH:55]=[CH:54][C:53]([C:56](Cl)=[O:57])=[CH:52][N:51]=1>>[CH3:1][O:2][C:3](=[O:39])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[C:31]([F:33])[C:30]([NH:34][C:56]([C:53]4[CH:52]=[N:51][C:50]([F:49])=[CH:55][CH:54]=4)=[O:57])=[CH:29][C:28]=3[C:35]([F:37])([F:38])[F:36])=[CH:25][CH:26]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

Reactant 4

HCID 6344Dichloromethane

HCID 31374Dimethylacetamide

HCID 146236022-Fluoropyridine-5-carbonyl chloride

HCID 178502394HCID 178502394, compound

Product 1

HCID 178502396HCID 178502396, compoundYield 103.9%

Procedure

To a solution of ((S)-1-{(S)-2-[4-(4′-amino-5′-fluoro-2′-trifluoromethyl-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (128 mg, 0.234 mmol; Preparation 39) in DCM (3 mL, 47 mmol) and DMA (0.3 mL, 3 mmol) was added 2-fluoropyridine-5-carbonyl chloride (37 mg, 0.234 mmol), and the resulting solution was stirred at RT overnight. The reaction mixture was concentrated by rotary evaporation to give the monoHCl salt of the title intermediate as a brownish oil (163 mg), which was used without further purification. (m/z): [M+H]+ calcd for C33H31F5N6O4 671.23 found 671.7.

Workup

concentrationThe reaction mixture was concentrated by rotary evaporation

Sources & evidence

ORD record: ord-c85862bf12554ba6819bfda90050d465
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921372B2

Reaction notes

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