Ammonium formate → HCID 89908187, compound

HRID 525741Notes

Reaction equation

HRID 525741 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[N:28](CC4C=CC(OC)=CC=4)[C:29]([CH3:32])=[CH:30][N:31]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1.C([O-])=O.[NH4+]>[Pd].CCO>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[NH:28][C:29]([CH3:32])=[CH:30][N:31]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 89906624HCID 89906624, compound

Product 1

HCID 89908187HCID 89908187, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Palladium on carbon 10% (5.63 mg) was added to a stirred mixture of (R)-6-(3-hydroxypyrrolidin-1-yl)-5-(1-(4-methoxybenzyl)-5-methyl-1H-imidazol-2-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 72.1, 300 mg, 0.053 mmol) and ammonium formate (33 mg, 0.529 mmol) in EtOH (5 mL) and the mixture was heated under reflux for 52 h. The RM was filtered through Hyflo® and the solvent was evaporated off under reduced pressure to give the crude product which was purified by SFC (Column DEAP, from 21% to 26% in 10 min) to afford the title compound as an amorphous solid. HPLC (Condition 4) tR=4.01 min, UPLC-MS (Condition 8) tR=0.76 min, m/z=448.2 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 1.66-1.92 (m, 2H), 2.11-2.29 (m, 2H), 2.91 (br.s, 1H), 3.28 (br.s, 2H), 3.38-3.50 (m, 2H), 4.22 (br. s, 1H), 4.89 (br.s, 1H), 6.63-6.74 (m, 1H), 6.87-6.96 (m, 1H), 7.35 (d, J=8.59 Hz, 2H), 7.88 (d, J=8.92 Hz, 2H), 8.12 (s, 1H), 8.77 (s, 1H), 10.22 (s, 1H), 11.85-12.17 (m, 1H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 52 h
  3. filtrationThe RM was filtered through Hyflo®
  4. customthe solvent was evaporated off under reduced pressure
  5. customto give the crude product which
  6. customwas purified by SFC (Column DEAP, from 21% to 26% in 10 min)

Sources & evidence

ORD record
ord-fb205ee7b634415180f51b62bd4762e4
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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