Ammonia → HCID 78103829, compound

HRID 1915871Notes

Reaction equation

HRID 1915871 reaction equation
[F:1][CH:2]1[CH2:8][N:7]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-])=O)[CH2:6][CH2:5][CH:4]([NH:18]C(=O)OC(C)(C)C)[CH2:3]1.C(OC([NH:33][C:34]1[S:38][C:37]([C:39]2[C:44]([F:45])=[CH:43][CH:42]=[CH:41][C:40]=2[F:46])=[N:36][C:35]=1[C:47](O)=[O:48])=O)(C)(C)C.CO.C(Cl)Cl.N>CO>[NH2:33][C:34]1[S:38][C:37]([C:39]2[C:44]([F:45])=[CH:43][CH:42]=[CH:41][C:40]=2[F:46])=[N:36][C:35]=1[C:47]([NH:15][C:10]1[CH:11]=[N:12][N:13]([CH3:14])[C:9]=1[N:7]1[CH2:6][CH2:5][CH:4]([NH2:18])[CH2:3][CH:2]([F:1])[CH2:8]1)=[O:48]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 21226129Dichloromethane methanolHCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86680065HCID 86680065, compound

Product 1

HCID 78103829HCID 78103829, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Following the procedure for Example 101, Intermediate 20, tert-butyl 6-fluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate and 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid from Example 25 gave, after silica gel column chromatography (0-10% MeOH/DCM, 1% 7 N ammonia in MeOH), a white solid (273 mg, 19% over three steps). Compound 154 was obtained as a single enantiomer from SFC chiral separation of the racemic mixture. 1H NMR (400 MHz, DMSO) δ 8.77 (s, 1H), 7.61-7.41 (m, 4H), 7.27 (dd, J=14.5, 5.8 Hz, 2H), 4.84-4.56 (m, 1H), 3.67 (d, J=7.4 Hz, 3H), 3.44-3.34 (m, 2H), 3.21-2.86 (m, 3H), 2.22-2.07 (m, 1H), 1.87 (ddt, J=34.3, 21.1, 7.4 Hz, 3H), 1.70-1.53 (m, 1H). MS (ESI) m/z: 466.1 [M+H+].

Workup

  1. customgave

Sources & evidence

ORD record
ord-00c6a5471fd5416f8cda7429a644b426
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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