6-(2,6-Difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acid → N-(5-((2S,5R,6S)-5-Amino-6-hydroxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinamide

HRID 521970Notes

Reaction equation

HRID 521970 reaction equation
[OH: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:21]([CH3:22])[N:20]=[CH:19][C:18]=2[N+:23]([O-])=O)[O:4][CH2:3]1.[F:26][C:27]1[CH:32]=[C:31]([O:33][CH2:34][CH2:35][O:36][CH3:37])[CH:30]=[C:29]([F:38])[C:28]=1[C:39]1[N:44]=[C:43]([C:45](O)=[O:46])[CH:42]=[CH:41][C:40]=1[F:48]>>[NH2:9][C@H:8]1[C@H:2]([OH:1])[CH2:3][O:4][C@H:5]([C:17]2[N:21]([CH3:22])[N:20]=[CH:19][C:18]=2[NH:23][C:45](=[O:46])[C:43]2[CH:42]=[CH:41][C:40]([F:48])=[C:39]([C:28]3[C:29]([F:38])=[CH:30][C:31]([O:33][CH2:34][CH2:35][O:36][CH3:37])=[CH:32][C:27]=3[F:26])[N:44]=2)[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 666523176-(2,6-Difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acidHCID 86713838tert-butyl ((3S,4R,7S)-3-hydroxy-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate2×

Product 1

HCID 73437752N-(5-((2S,5R,6S)-5-Amino-6-hydroxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinamideYield 71%

Procedure

Following the procedure for Example 111 starting from tert-butyl ((3S,4R,7S)-3-hydroxy-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 94), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 6-(2,6-difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 191 as a white solid (73 mg, 71%). 1H NMR (400 MHz, d6-DMSO) δ 10.22 (s, 1H), 8.25 (dd, J=8.6, 4.0 Hz, 1H), 8.12 (t, J=8.9 Hz, 1H), 7.82 (s, 1H), 6.97 (d, J=10.2 Hz, 2H), 4.79 (dd, J=10.8, 3.4 Hz, 2H), 4.26-4.20 (m, 2H), 3.90-3.67 (m, 4H), 3.73-3.67 (m, 2H), 3.63 (dd, J=12.8, 5.8 Hz, 1H), 3.62-3.02 (m, 3H), 2.73-2.64 (m, 1H), 2.00-1.92 (m, 1H), 1.92-1.79 (m, 1H), 1.79-1.72 (m, 1H), 1.55-1.42 (m, 1H). Alkyl NH2 not observed. LCMS (ES+) m/z 536 (M+1).

Sources & evidence

ORD record
ord-6f24e49a74674501a73556cdf0d63e87
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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