Trifluoroacetic acid → N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-ethylthiophene-2-carboxamide

HRID 1842611Notes

Reaction equation

HRID 1842611 reaction equation
[F:1][CH:2]([F:39])[O:3][C:4]1[CH:5]=[N:6][C:7]2[N:8]([N:10]=[CH:11][C:12]=2[C:13]2[CH:14]=[C:15]([C:20]([NH:22][C@H:23]3[C:28]([F:30])([F:29])[CH2:27][CH2:26][CH2:25][C@H:24]3[NH:31]C(=O)OC(C)(C)C)=[O:21])[S:16][C:17]=2[CH2:18][CH3:19])[CH:9]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[NH2:31][C@H:24]1[C@@H:23]([NH:22][C:20]([C:15]2[S:16][C:17]([CH2:18][CH3:19])=[C:13]([C:12]3[CH:11]=[N:10][N:8]4[CH:9]=[C:4]([O:3][CH:2]([F:1])[F:39])[CH:5]=[N:6][C:7]=34)[CH:14]=2)=[O:21])[C:28]([F:29])([F:30])[CH2:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 68304376tert-Butyl {(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-ethylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate

Product 1

HCID 86692129N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-ethylthiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl {(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-ethylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate (0.037 g, 0.064 mmol) was dissolved in dichloromethane (0.639 mL) and trifluoroacetic acid (0.250 mL, 3.24 mmol) was added. The reaction was stirred at room temperature for 2 h. 5N NaOH (aq) was added and extracted 3× with dichloromethane. The organic layers were combined, dried with sodium sulfate, filtered, and concentrated. The material was purified by column chromatography (0-5% MeOH/DCM) to give the title compound. LRMS (APCI) calc'd for (C20H21F4N5O2S) [M+H]+, 472.1; found 472.1. 1H NMR (CD3OD, 500 MHz) δ 9.04 (d, J=2.4, 1H), 8.59 (d, J=2.4, 1H), 8.35 (s, 1H), 8.13 (s, 1H), 6.97 (t, J=72.5, 1H), 3.24 (s, 1H), 3.02 (q, J=7.5, 2H), 2.15 (s, 1H), 1.48-1.99 (m, 4H), 1.32 (t, 3H), 1.00-1.18 (m, 2H).

Workup

  1. extractionextracted 3× with dichloromethane
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe material was purified by column chromatography (0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-a0616e5299fb42c6b62da8936d61e34a
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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