Acetic Acid → HCID 59149834, compound

HRID 1675115Notes

Reaction equation

HRID 1675115 reaction equation
[B-]C#N.[Na+].[F:5][C:6]1([F:26])[CH2:12][N:11]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([C:22]([F:25])([F:24])[F:23])=[N:20][N:21]=3)[N:18]=2)[CH2:10][CH2:9][NH:8][CH2:7]1.[F:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1.C(O)(=O)C>CO>[F:26][C:6]1([F:5])[CH2:12][N:11]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([C:22]([F:24])([F:25])[F:23])=[N:20][N:21]=3)[N:18]=2)[CH2:10][CH2:9][N:8]([CH2:32][C:31]2[CH:34]=[CH:35][C:28]([F:27])=[CH:29][CH:30]=2)[CH2:7]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 20587905Sodium cyanoborohydride [MI]HCID 673406806-(6,6-Difluorohexahydro-1H-1,4-diazepin-1-yl)-3-(trifluoromethyl)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 59149834HCID 59149834, compoundYield 57.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
21 °C

Procedure

Sodium cyanotrihydroborate (58.5 mg, 0.93 mmol) was added to a stirred mixture of 6-(6,6-difluoro-1,4-diazepan-1-yl)-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (200 mg, 0.62 mmol), 4-fluorobenzaldehyde (93 mg, 0.75 mmol) and acetic acid (71.1 μl, 1.24 mmol) in methanol (10 mL) at room temperature. The resulting mixture was stirred at 21° C. for 20 hours. The reaction mixture was concentrated to dryness, diluted with methanol and a few drops of 7M ammonia in methanol were added. The mixture was concentrated to dryness, the residue was diluted with DCM and the salts were filtered off. The filtrate was concentrated and purified by flash chromatography on silica gel eluting with 0 to 20% acetonitrile in DCM. Product-containing fractions were concentrated to give to give 6-[6,6-difluoro-4-(4-fluorobenzyl)-1,4-diazepan-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (154 mg, 55%).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. additiondiluted with methanol and a few drops of 7M ammonia in methanol
  3. additionwere added
  4. concentrationThe mixture was concentrated to dryness
  5. additionthe residue was diluted with DCM
  6. filtrationthe salts were filtered off
  7. concentrationThe filtrate was concentrated
  8. custompurified by flash chromatography on silica gel eluting with 0 to 20% acetonitrile in DCM
  9. concentrationProduct-containing fractions were concentrated
  10. customto give

Sources & evidence

ORD record
ord-485366c60a8a4c5e968043006668c8eb
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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