Trifluoroacetic acid → Propane-1-sulfonic acid {2,4-difluoro-3-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide

HRID 60108Notes

Reaction equation

HRID 60108 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[C:21]4[C:27]([C:28](=[O:44])[C:29]5[C:34]([F:35])=[CH:33][CH:32]=[C:31]([NH:36][S:37]([CH2:40][CH2:41][CH3:42])(=[O:39])=[O:38])[C:30]=5[F:43])=[CH:26][NH:25][C:22]4=[N:23][CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[F:43][C:30]1[C:29]([C:28]([C:27]2[C:21]3[C:22](=[N:23][CH:24]=[C:19]([C:17]4[CH:16]=[N:15][N:14]([CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)[CH:18]=4)[CH:20]=3)[NH:25][CH:26]=2)=[O:44])=[C:34]([F:35])[CH:33]=[CH:32][C:31]=1[NH:36][S:37]([CH2:40][CH2:41][CH3:42])(=[O:38])=[O:39]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 532621584-(4-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 53247267Propane-1-sulfonic acid {2,4-difluoro-3-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amideYield 16.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a reaction flask, 4-(4-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (P-1001, 42.0 mg, 0.067 mmol) is dissolved in 9.0 mL of dichloromethane and 1.0 mL of trifluoroacetic acid and the reaction is stirred at room temperature for 2 hours. Aqueous saturated sodium bicarbonate is added and the mixture is extracted with ethyl acetate. The aqueous layer is frozen and lyophilized and the residue is suspended in tetrahydrofuran and sonicated. The mixture is filtered twice and the filtrate is concentrated under vacuum. The resulting material is purified by reverse phase HPLC, eluting with acetonitrile/water with 0.1% formic acid, 5-47.5% acetonitrile over 40 minutes. Appropriate fractions are combined and dried by lyophilization to provide the desired compound as a white solid (P-1002, 5.7 mg). MS (ESI) [M+H+]+=529.0.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. temperatureThe aqueous layer is frozen
  3. customsonicated
  4. filtrationThe mixture is filtered twice
  5. concentrationthe filtrate is concentrated under vacuum
  6. customThe resulting material is purified by reverse phase HPLC
  7. washeluting with acetonitrile/water with 0.1% formic acid, 5-47.5% acetonitrile over 40 minutes
  8. customdried by lyophilization

Sources & evidence

ORD record
ord-339f9224fb2a48f28ac07fe5d6d5437e
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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