Cyanoacetic acid → HCID 86714532, compound

HRID 409154Notes

Reaction equation

HRID 409154 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-36bf683d86f64b659e2df536df78280d
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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