Trifluoroacetic acid → HCID 86692130, compound

HRID 1842614Notes

Reaction equation

HRID 1842614 reaction equation
C(OC(=O)[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][C:10]([F:15])([F:14])[C@@H:9]1[NH:16][C:17]([C:19]1[S:20][C:21]([CH2:39][CH3:40])=[C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[C:31]([O:33][CH2:34][C:35]([F:38])([F:37])[F:36])[CH:30]=[N:29][C:28]=23)[CH:23]=1)=[O:18])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C@H:8]1[C@@H:9]([NH:16][C:17]([C:19]2[S:20][C:21]([CH2:39][CH3:40])=[C:22]([C:24]3[CH:25]=[N:26][N:27]4[CH:32]=[C:31]([O:33][CH2:34][C:35]([F:38])([F:37])[F:36])[CH:30]=[N:29][C:28]=34)[CH:23]=2)=[O:18])[C:10]([F:14])([F:15])[CH2:11][CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89752097HCID 89752097, compound

Product 1

HCID 86692130HCID 86692130, compoundYield 82.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

tert-Butyl{(1R,2R)-2-[({5-ethyl-4-[6-(2,2,2-trifluoroethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]thiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate (34.0 mg, 0.056 mmol) was dissolved in dichloromethane (1.0 mL) and trifluoroacetic acid (0.100 mL, 1.30 mmol) was added. The reaction was stirred at 40° C. for 2 h. The reaction mixture was quenched with 1N KOH in MeOH and concentrated under reduced pressure. The residue was mixed with water and extracted 3× with dichloromethane. The organic layers were combined, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (0-20% MeOH/DCM) to give the title compound (23.0 mg, 0.046 mmol). LRMS (APCI) calc'd for (C21H22F5N5O2S) [M+H]+, 504.1; found 504.0. 1H NMR (CDCl3, 500 MHz) δ 8.48 (s, 1H), 8.37 (s, 1H), 8.15 (s, 1H), 7.88 (s, 1H), 7.03 (s, 1H), 4.52 (m, 1H), 4.43 (d, J=7.8, 2H), 3.36 (s, 1H), 2.96 (q, J=7.2, 2H), 2.17 (s, 1H), 1.48-2.02 (m, 5H), 1.33 (t, J=7.3, 3H).

Workup

  1. customThe reaction mixture was quenched with 1N KOH in MeOH
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was mixed with water
  4. extractionextracted 3× with dichloromethane
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-9d639d36e33447378f0b9c422b300d56
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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