Nitrogen → HCID 89306486, compound

HRID 404195Notes

Reaction equation

HRID 404195 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-9619e14b93454aeba2fc919c5c33b48e
Source dataset
uspto-grants-2014_06
Patent number
US08748461B2

Reaction notes

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