Diisopropylethylamine → (R)-2-(3-(4-amino-3-(4-(2,3-difluorophenoxy)-2-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-methylpent-2-enenitrile

HRID 409148Notes

Reaction equation

HRID 409148 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]([C@@H:21]3[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]3)[N:12]=2)=[C:7]([F:27])[CH:6]=1.[C:33]([C:35](=[CH:39][CH:40]([CH3:42])[CH3:41])[C:36](O)=[O:37])#[N:34].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH2:20][C:18]1[N:17]=[CH:16][N:15]=[C:14]2[N:13]([C@@H:21]3[CH2:26][CH2:25][CH2:24][N:23]([C:36]([C:35](=[CH:39][CH:40]([CH3:42])[CH3:41])[C:33]#[N:34])=[O:37])[CH2:22]3)[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 4

HCID 81531DiisopropylethylamineHCID 2925472-Cyano-4-methylpent-2-enoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71015155(R)-3-(4-(2,3-difluorophenoxy)-2-fluorophenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 71015828(R)-2-(3-(4-amino-3-(4-(2,3-difluorophenoxy)-2-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-methylpent-2-enenitrileYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (R)-3-(4-(2,3-difluorophenoxy)-2-fluorophenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.23 mmol, 1.0 eq), 2-cyano-4-methyl-pent-2-enoic acid (38 mg, 0.27 mmol, 1.2 eq) and DIEA (88 mg, 0.68 mmol, 3.0 eq) in 10 ml DCM was added HATU (130 mg, 0.34 mmol, 1.5 eq). The reaction mixture was stirred for 4 h at RT under N2. The mixture was purified by Pre-HPLC to give the title compound (25 mg 40% yield). LCMS: m/z+ (562.2) (M+H)+ 1HNMR (400 MHz, CDCl3): δ 0.784˜1.186 (m, 7H), 1.765˜2.254 (m, 5H), 2.861˜4.937 (m, 4H), 6.218 (m, 0.4H), 6.857˜7.600 (m, 6H), 8.255 (s, 1H) and 9.888 (m, 1H).

Workup

  1. customThe mixture was purified by Pre-HPLC

Sources & evidence

ORD record
ord-ffa02d3303574fbaa39eeca67dd1d1da
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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