Cyanoacetic acid → HCID 86714532, compound

HRID 1187639Notes

Reaction equation

HRID 1187639 reaction equation
[F:1][C:2]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[N:17][C:18]=3[NH2:20])[N:13]([CH2:21][C@@H:22]3[CH2:26][CH2:25][CH2:24][NH:23]3)[N:12]=2)=[C:7]([F:27])[CH:6]=1.[C:33]([CH2:35][C:36](O)=[O:37])#[N:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[NH2:20][C:18]1[N:17]=[CH:16][N:15]=[C:14]2[N:13]([CH2:21][C@@H:22]3[CH2:26][CH2:25][CH2:24][N:23]3[C:36](=[O:37])[CH2:35][C:33]#[N:34])[N:12]=[C:11]([C:8]3[CH:9]=[CH:10][C:5]([O:4][C:3]4[CH:28]=[CH:29][CH:30]=[C:31]([F:32])[C:2]=4[F:1])=[CH:6][C:7]=3[F:27])[C:19]=12

Participants

6

Reactant 3

HCID 9740Cyanoacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86714533HCID 86714533, compound

Product 1

HCID 86714532HCID 86714532, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-(4-(2,3-difluorophenoxy)-2-fluorophenyl)-1-((S)-pyrrolidin-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.4 g Crude, 3.65 mmol, 1.00 equiv), 2-cyanoacetic acid (0.47 g, 5.48 mmol, 1.50 equiv), HATU (2.08 g, 5.48 mmol, 1.50 equiv), TEA (2.54 ml, 18.25 mmol, 5.00 equiv) in DCM (40 mL) was stirred overnight at room temperature. The resulting mixture was diluted with water, and extracted with DCM. The DCM layers were combined and washed with brine, dried over Na2SO4 and concentrated. The residue was submitted to flash chromatography (SiO2, PE: EtOAc=2:1 to 1:1) to give 1.28 g (69%) of 3-((S)-2-((4-amino-3-(4-(2,3-difluorophenoxy)-2-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidin-1-yl)-3-oxopropanenitrile as a yellow solid.

Workup

  1. extractionextracted with DCM
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8cf31f72bf3b443cb3c9697a6a22cab0
Source dataset
uspto-grants-2014_03
Patent number
US08673925B1

Reaction notes

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