Diisopropylethylamine → 1-methyl-3-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 1909992Notes

Reaction equation

HRID 1909992 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[N:16][C:17]=4[NH2:19])[N:12]([CH3:20])[N:11]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH3:21][N:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[CH2:27][C:28](O)=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O>[CH3:20][N:12]1[C:13]2=[N:14][CH:15]=[N:16][C:17]([NH2:19])=[C:18]2[C:10]([C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[N:1]([C:28](=[O:29])[CH2:27][C:23]2[N:22]([CH3:21])[CH:26]=[CH:25][CH:24]=2)[CH2:2][CH2:3]3)=[N:11]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 890951-Methyl-1H-pyrrole-2-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668235513-(2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 534682571-methyl-3-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 45.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 3-(2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.330 mmol), (1-methyl-1H-pyrrol-2-yl)acetic acid (46 mg, 0.33 mmol), HATU (126 mg, 0.330 mmol), and DIEA (0.231 mL, 1.321 mmol) was stirred at room temperature overnight. LCMS indicated good converison, so the crude was poured into water and stirred for 30 minutes. The precipitate that formed was collected by filtration, washed with water and dried at the pump for 30 minutes. The crude was adsorbed onto silica and purified by flash chromatography (0-10% methanol in DCM) to afford 1-methyl-3-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine (57.9 mg, 0.149 mmol, 45.2% yield) as a white solid. LC-MS (ES) m/z=388 [M+H]+. 1H NMR (400 MHz, DMSO-d6) 3.25 (m, 2H), 3.55 (s, 3H), 3.86-3.90 (m, 2H), 3.94 (s, 3H), 4.21-4.32 (m, 2H), 5.86-5.93 (m, 2H), 6.66-6.71 (m, 1H), 7.41-7.48 (m, 1H), 7.49-7.53 (m, 1H), 8.13-8.22 (m, 1H), 8.23-8.27 (m, 1H). Note: NH's are not observed in the NMR spectrum.

Workup

  1. customThe precipitate that formed
  2. filtrationwas collected by filtration
  3. washwashed with water
  4. customdried at the pump for 30 minutes
  5. custompurified by flash chromatography (0-10% methanol in DCM)

Sources & evidence

ORD record
ord-1d62e8c639bc4af2a333807210b3d2b8
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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