5-(Tert-butoxycarbonylamino)-2-(2,3-difluorophenyl)thiazole-4-carboxylic acid → 5-Amino-N-[5-[(2S,5R,6R)-5-amino-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]-2-(2,3-difluorophenyl)thiazole-4-carboxamide

HRID 521962Notes

Reaction equation

HRID 521962 reaction equation
[F:1][C@H:2]1[C@H:8]([NH:9]C(=O)OC(C)(C)C)[CH2:7][CH2:6][C@@H:5]([C:17]2[N:18]([CH3:25])[N:19]=[CH:20][C:21]=2[N+:22]([O-])=O)[O:4][CH2:3]1.BrC1SC(NC(=O)OC(C)(C)C)=C(C(=O)NC2C=NN(C)C=2[C@@H]2CC[C@@H](NC(OC(C)(C)C)=O)[C@@H](F)CO2)N=1.C(OC([NH:72][C:73]1[S:77][C:76]([C:78]2[CH:83]=[CH:82][CH:81]=[C:80]([F:84])[C:79]=2[F:85])=[N:75][C:74]=1[C:86](O)=[O:87])=O)(C)(C)C>>[NH2:72][C:73]1[S:77][C:76]([C:78]2[CH:83]=[CH:82][CH:81]=[C:80]([F:84])[C:79]=2[F:85])=[N:75][C:74]=1[C:86]([NH:22][C:21]1[CH:20]=[N:19][N:18]([CH3:25])[C:17]=1[C@@H:5]1[CH2:6][CH2:7][C@@H:8]([NH2:9])[C@@H:2]([F:1])[CH2:3][O:4]1)=[O:87]

Participants

4

Reactant 3

HCID 581821445-(Tert-butoxycarbonylamino)-2-(2,3-difluorophenyl)thiazole-4-carboxylic acidHCID 86713830tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamateHCID 86713841tert-butyl ((3S,4R,7S)-3-fluoro-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate

Product 1

HCID 900725115-Amino-N-[5-[(2S,5R,6R)-5-amino-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]-2-(2,3-difluorophenyl)thiazole-4-carboxamide

Procedure

Following the procedure for Example 111 starting from tert-butyl N-[(3S,4R,7S)-3-fluoro-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-yl]carbamate (Intermediate 88), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 5-(tert-butoxycarbonylamino)-2-(2,3-difluorophenyl)thiazole-4-carboxylic acid (Example 25) gave 181 as the hydrochloride salt as a pale pink solid (30 mg, 38% over three steps). 1H NMR (400 MHz, d6-DMSO) δ 9.42 (s, 1H), 8.54-8.41 (m, 4H), 7.96-7.89 (m, 1H), 7.67 (s, 1H), 7.50-7.39 (m, 3H), 5.28 (m, 1H), 4.84 (d, J=10.4 Hz, 1H), 4.33-4.17 (m, 1H), 4.11-3.99 (m, 1H), 3.78 (s, 3H), 3.74-3.52 (m, 1H), 2.16-1.81 (m, 4H). LCMS (ES+) m/z 467 (M+1).

Sources & evidence

ORD record
ord-31beba2e443441f0ab589f1d3d71bdba
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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