Trifluoroacetic acid → 2-(3-Chloro-4-fluorophenyl)-6-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

HRID 920832Notes

Reaction equation

HRID 920832 reaction equation
[C:1]([C:4]1[C:5]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[C:25]([Cl:30])[CH:24]=2)=[N:6][N:7]2[CH2:12][CH:11]([CH:13]3[CH2:15][CH2:14]3)[N:10](C(OC(C)(C)C)=O)[CH2:9][C:8]=12)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:30][C:25]1[CH:24]=[C:23]([C:5]2[C:4]([C:1]([NH2:2])=[O:3])=[C:8]3[CH2:9][NH:10][CH:11]([CH:13]4[CH2:14][CH2:15]4)[CH2:12][N:7]3[N:6]=2)[CH:28]=[CH:27][C:26]=1[F:29]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118071213tert-Butyl 3-carbamoyl-2-(3-chloro-4-fluorophenyl)-6-cyclopropyl-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate

Product 1

HCID 1180617232-(3-Chloro-4-fluorophenyl)-6-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamideYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of Intermediate 348H (0.43 g, 0.989 mmol) in DCM (8.0 mL) was added TFA (4.0 mL, 51.9 mmol) and the resulting solution was stirred at RT for 2 h. The reaction mixture was concentrated and the residue was extracted with DCM (10 mL), and washed successively with water, a saturated aq. NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure to afford Intermediate 3481 as an off-white solid (0.3 g, 67%). MS(ES): m/z=335 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.80-7.91 (m, 1H), 7.64-7.70 (m, 1H), 7.35-7.50 (m, 1H), 7.02-7.29 (m, 2H), 4.12-4.25 (m, 2H), 3.93 (d, J=16.56 Hz, 1H), 3.68-3.81 (m, 2H), 2.40 (br. s., 1H), 0.82-0.98 (m, 1H), 0.48 (d, J=8.03 Hz, 2H), 0.37 (d, J=5.02 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionthe residue was extracted with DCM (10 mL)
  3. washwashed successively with water
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-727a1c4fe2c04ebd9fdf1af73dd35478
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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