Trifluoroacetic acid → Methyl-3-(5-{[(1R,6R)-6-amino-2,2-difluorocyclohexyl]carbamoyl}-2-methylthiophen-3-yl)pyrazolo[1,5-a]pyrimidine-6-carboxylate

HRID 1842605Notes

Reaction equation

HRID 1842605 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]([CH3:40])=[C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[C:31]([C:33](OC)([O:36]C)[O:34][CH3:35])[CH:30]=[N:29][C:28]=23)[CH:23]=1)=[O:18])(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:35][O:34][C:33]([C:31]1[CH:30]=[N:29][C:28]2[N:27]([N:26]=[CH:25][C:24]=2[C:22]2[CH:23]=[C:19]([C:17](=[O:18])[NH:16][C@@H:9]3[C@H:8]([NH2:7])[CH2:13][CH2:12][CH2:11][C:10]3([F:14])[F:15])[S:20][C:21]=2[CH3:40])[CH:32]=1)=[O:36]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 131732414tert-Butyl{(1R,2R)-3,3-difluoro-2-[({5-methyl-4-[6-(trimethoxymethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophen-2-yl}carbonyl)amino]cyclohexyl}carbamate

Product 1

HCID 68305168Methyl-3-(5-{[(1R,6R)-6-amino-2,2-difluorocyclohexyl]carbamoyl}-2-methylthiophen-3-yl)pyrazolo[1,5-a]pyrimidine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl{(1R,2R)-3,3-difluoro-2-[({5-methyl-4-[6-(trimethoxymethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophen-2-yl}carbonyl)amino]cyclohexyl}carbamate (45 mg, 0.076 mmol) was dissolved in dichloromethane (2 mL) and trifluoroacetic acid (275 μL, 3.55 mmol) added. The reaction mixture was stirred at room temperature for 1 h, neutralized with saturated sodium bicarbonate (aq) and extracted 3× with dichloromethane. The organic layers were combined and dried with sodium sulfate, concentrated and purified by column chromatography (0-10% MeOH/DCM) to afford the title compound (quantitative yield). LRMS (APCI) calc'd for (C20H21F2N5O3S) [M+H]+, 450.1; found 450.1. 1H NMR (CDCl3, 500 MHz) δ 9.33 (s, 1H), 9.03 (s, 1H), 8.40 (s, 1H), 7.93 (s, 1H), 6.98 (d, J=8.1, 1H), 4.45 (d, J=25.3, 1H), 4.01 (s, 3H), 3.34 (s, 1H), 2.60 (s, 3H), 2.18 (s, 1H), 1.70-1.90 (s, 5H).

Workup

  1. extractionextracted 3× with dichloromethane
  2. dry with materialdried with sodium sulfate
  3. concentrationconcentrated
  4. custompurified by column chromatography (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-f727375e30f54523881e02ef7ecf8485
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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