Diisopropylethylamine → 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(5-methanesulfonyl-furan-2-yl)-cyclopropyl]-amide

HRID 2172970Notes

Reaction equation

HRID 2172970 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.Cl.[CH3:30][S:31]([C:34]1[O:38][C:37]([C:39]2([NH2:42])[CH2:41][CH2:40]2)=[CH:36][CH:35]=1)(=[O:33])=[O:32].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C=O)C.[Cl-].[NH4+]>[CH3:30][S:31]([C:34]1[O:38][C:37]([C:39]2([NH:42][C:17]([C:16]3[C:11]4[CH:10]=[N:9][N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[C:12]=4[CH:13]=[N:14][CH:15]=3)=[O:19])[CH2:41][CH2:40]2)=[CH:36][CH:35]=1)(=[O:33])=[O:32]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 592781371-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acidHCID 671158911-(5-Methanesulfonyl-furan-2-yl)-cyclopropylamine hydrochloride salt

Product 1

HCID 529168871-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(5-methanesulfonyl-furan-2-yl)-cyclopropyl]-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a stirred mixture of 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (0.310 g, 1.21 mmol), N,N-diisopropylethylamine (0.630 mL, 3.62 mmol) and 1-(5-methanesulfonyl-furan-2-yl)-cyclopropylamine-hydrochloride salt (364 mg, 1.53 mmol) in DMF (30 mL) is added (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP) (0.650 g, 1.25 mmol). After 18 hours, the mixture is diluted with saturated aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (4×30 mL). The combined organic layers are washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-100% ethyl acetate in hexanes to afford the title compound as a solid.

Workup

  1. extractionextracted with ethyl acetate (4×30 mL)
  2. washThe combined organic layers are washed with brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-101e6df202714fd49388f1b98e7ea33e
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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