Nitrogen → HCID 89306486, compound

HRID 1506606Notes

Reaction equation

HRID 1506606 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:34])([CH2:28][N:29]1[CH:33]=[N:32][N:31]=[N:30]1)[C:10]([C:13]1[N:18]=[CH:17][C:16]([O:19][C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][N:21]=2)=[CH:15][CH:14]=1)([F:12])[F:11].Cl.[CH3:36][O:37][NH2:38].N#N>CCO>[CH3:36][O:37]/[N:38]=[CH:24]/[C:23]1[CH:26]=[CH:27][C:20]([O:19][C:16]2[CH:17]=[N:18][C:13]([C:10]([F:12])([F:11])[C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])([OH:34])[CH2:28][N:29]3[CH:33]=[N:32][N:31]=[N:30]3)=[CH:14][CH:15]=2)=[N:21][CH:22]=1

Participants

5

Reactant 3

HCID 947NitrogenHCID 521874O-Methylhydroxylamine hydrochlorideHCID 86675115HCID 86675115, compound

Product 1

HCID 89306486HCID 89306486, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a magnetically stirred mixture of 6-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)nicotinaldehyde (101) (60 mg, 0.126 mmol) in dry EtOH (1.265 mL) was added O-Methylhydroxylamine hydrochloride (21.13 mg, 0.253 mmol) in a 5 mL vial under N2 atmosphere. The reaction mixture was stirred at RT overnight. The reaction mixture was evaporated and the crude residue was purified on silica (ISCO, 12 gram column, gradient to 75% EtOAc/Hexanes over 25 minutes) to afford the title compound. Yield=18 mg (26.9%) of a white foam. 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.47 (d, J=2.5 Hz, 1H), 8.19 (d, J=2.3 Hz, 1H), 8.11 (dd, J=8.7, 2.4 Hz, 1H), 8.04 (s, 1H), 7.67 (dd, J=8.7, 2.6 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.45 (s, 1H), 7.36 (td, J=8.8, 6.4 Hz, 1H), 7.05 (d, J=8.5 Hz, 1H), 6.83-6.73 (m, 1H), 6.73-6.64 (m, 1H), 5.63 (d, J=14.3 Hz, 1H), 5.10 (d, J=14.3 Hz, 1H), 3.99 (s, 3H). 1H-decoupled 19F NMR (376 MHz, CDCl3) δ−103.20 (d, J=17.7 Hz), −103.89 (ddd, J=31.3, 21.1, 13.6 Hz), −108.11 (d, J=9.5 Hz), −110.21 (d, J=45.0 Hz), −110.90 (d, J=45.0 Hz). MS (ESI): m/z 504.2 (M+H)+.

Workup

  1. customThe reaction mixture was evaporated
  2. customthe crude residue was purified on silica (ISCO, 12 gram column, gradient to 75% EtOAc/Hexanes over 25 minutes)

Sources & evidence

ORD record
ord-3299815a0d164c2c9e391bc1bff8e6e5
Source dataset
uspto-grants-2015_12
Patent number
US09220265B2

Reaction notes

Loading…