Dimethylformamide → HCID 92131116, compound

HRID 1478817Notes

Reaction equation

HRID 1478817 reaction equation
[F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]3[N:14]=[N:15][C:16]([C:17](O)=[O:18])=[C:12]3[CH2:11][CH2:10][CH2:9][C:8]=2[CH:20]=1.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:34][C:35]1[C:36](=[O:48])[N:37]([CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)[N:38]([CH3:41])[C:39]=1[CH3:40].C(N(CC)CC)C>C(Cl)Cl.O>[CH:42]1([N:37]2[C:36](=[O:48])[C:35]([NH:34][C:17]([C:16]3[N:15]=[N:14][N:13]4[C:7]5[CH:6]=[CH:5][C:4]([O:3][C:2]([F:21])([F:22])[F:1])=[CH:20][C:8]=5[CH2:9][CH2:10][CH2:11][C:12]=34)=[O:18])=[C:39]([CH3:40])[N:38]2[CH3:41])[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 612730214-amino-2-cyclohexyl-1,5-dimethyl-2,3-dihydro-1H-pyrazol-3-one2×HCID 118513287HCID 118513287, compound

Product 1

HCID 92131116HCID 92131116, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 8-(trifluoromethoxy)-5,6-dihydro-4H-benzo[f][1,2,3]triazolo[1,5-a]azepine-3-carboxylic acid (169 mg, 0.540 mmol) in dry DCM (2 mL) under nitrogen was added oxalyl chloride (0.052 mL, 0.593 mmol) and DMF (0.084 mL, 1.079 mmol) and the mixture was stirred for 15 mins. 4-Amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate A) (124 mg, 0.593 mmol) was added followed by triethylamine (0.226 mL, 1.619 mmol) and the mixture was stirred at RT for 16 hrs. The resultant mixture was diluted with DCM and water and stirred vigorously. The mixture was passed through a phase separating cartridge and the organic portion was concentrated under reduced pressure to give a yellow oil. The oil was absorbed onto silica and purified by chromatography eluting with 100% TBME. The product fractions were combined and concentrated under reduced pressure to give a glassy solid which was recrystallised from 1:1 diethylether:EtOAc. The resulting crystals were filtered under gravity to give the title compound as a white solid.

Workup

  1. stirringthe mixture was stirred at RT for 16 hrs
  2. stirringstirred vigorously
  3. customseparating cartridge
  4. concentrationthe organic portion was concentrated under reduced pressure
  5. customto give a yellow oil
  6. customThe oil was absorbed onto silica
  7. custompurified by chromatography
  8. washeluting with 100% TBME
  9. concentrationconcentrated under reduced pressure
  10. customto give a glassy solid which
  11. customwas recrystallised from 1:1 diethylether
  12. filtrationThe resulting crystals were filtered under gravity

Sources & evidence

ORD record
ord-577a528977074e6fb8a6f305f6dda2f4
Source dataset
uspto-grants-2016_08
Patent number
US09403833B2

Reaction notes

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