Trifluoroacetic acid → HCID 178494163, compound

HRID 2177661Notes

Reaction equation

HRID 2177661 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][C:15]2[CH:20]=[N:19][CH:18]=[C:17]([NH:21][C:22]3[N:23](C(OC(C)(C)C)=O)[N:24]=[C:25]([C:27]4[C:28]([O:34][CH3:35])=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=4)[CH:26]=3)[N:16]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:35][O:34][C:28]1[C:27]([C:25]2[CH:26]=[C:22]([NH:21][C:17]3[CH:18]=[N:19][CH:20]=[C:15]([O:14][C@@H:10]4[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]4)[N:16]=3)[NH:23][N:24]=2)=[CH:32][CH:31]=[C:30]([CH3:33])[N:29]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86690537HCID 86690537, compound

Product 1

HCID 178494163HCID 178494163, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (R)-3-{6-[2-tert-butoxycarbonyl-5-(2-methoxy-6-methyl-pyridin-3-yl)-2H-pyrazol-3-ylamino]-pyrazin-2-yloxy}-piperidine-1-carboxylic acid tert-butyl ester (13.0 g, 22.3 mmol) in dichloromethane (150 mL) is added a solution of trifluoroacetic acid (12.4 mL, 167 mmol) dichloromethane (20 mL) over a period of 5 min at 0° C. The reaction is allowed to warm to room temperature and stirred for 3 h. The reaction is diluted with dichloromethane (1000 mL), followed by addition of saturated sodium bicarbonate solution (250 mL) and then stirred for 4 h. The organic portion is separated and dried over anhydrous sodium sulfate, filtered, and evaporated. The resulting material is crystallized from isopropanol to obtain the desired product. Yield=7.2 g (85%). 1H NMR (400 MHz, DMSO-d6) δ 12.40 (s, 1H), 9.71 (s, 1H), 8.02 (d, J=7.6 Hz, 1H), 7.97 (s, 1H), 7.46)(s, 1H), 6.93 (d, J=7.6 Hz, 1H), 6.91 (s, 1H), 4.94-4.86 (m, 1H), 3.97 (s, 3H), 3.20-3.13 (m, 1H), 2.83-2.75 (m, 1H), 2.57 (dd, J=12.0, 84 Hz, 1H), 2.53-2.45 (m obscured, 1H), 2.42 (s, 3H), 2.15-2.05 (m, 1H), 1.71-1.63 (m, 1H), 1.60-1.49 (m, 1H), 1.49-1.40 (m, 1H); ES/MS m/z 382.5 [M+H]+.

Workup

  1. stirringstirred for 4 h
  2. customThe organic portion is separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe resulting material is crystallized from isopropanol

Sources & evidence

ORD record
ord-4b867bc91d9f4b6c83950e3036a62465
Source dataset
uspto-grants-2015_06
Patent number
US09067920B2

Reaction notes

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