Diisopropylethylamine → 7-methyl-5-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1910022Notes

Reaction equation

HRID 1910022 reaction equation
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.N1C2C(=CC(C3C4C(N)=NC=NC=4N(C)C=3)=CC=2)CC1.CN([C:46]([O:50]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[CH2:68][N:69]([CH:73]([CH3:75])[CH3:74])[CH:70]([CH3:72])C>O>[CH3:22][N:14]1[C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH2:21])[C:20]=2[C:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[N:3]([C:46](=[O:50])[CH2:75][C:73]2[N:69]([CH3:68])[CH:70]=[CH:72][CH:74]=2)[CH2:4][CH2:5]3)=[CH:13]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668234705-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochlorideHCID 668234715-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 668235177-methyl-5-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 44.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (250 mg, 0.739 mmol), 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine.2HCl (250 mg, 0.739 mmol), HATU (281 mg, 0.739 mmol), DIEA (0.516 mL, 2.96 mmol) was stirred at room temperature overnight. The reaction mixture was poured into 20 mL water and stirred for 30 mins. The grey precipitate was filtered, washed with water (10 mL) and dried for an hour at the pump. The residue was adsorbed onto silica and purified by flash chromatography (0-10% MeOH in DCM, 24-g column) to afford 7-methyl-5-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (128 mg, 44.8% yield) as a white solid. LC-MS (ES) m/z=387 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.23 (t, J=8.34 Hz, 2H), 3.54 (s, 3H), 3.73 (s, 3H), 3.86 (s, 2H), 4.25 (t, J=8.59 Hz, 2H), 5.84-5.94 (m, 2H), 5.94-6.32 (m, 2H), 6.68 (t, J=2.15 Hz, 1H), 7.14-7.29 (m, 2H), 7.31 (s, 1H), 8.08-8.20 (m, 2H). An additional crop of material was obtained from crystals observed in the filtrate after standing overnight. The liquid was filtered and the residue washed with water and dried at the pump to yield a second crop of 7-methyl-5-{1-[(1-methyl-1H-pyrrol-2-yl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (65 mg, 22.76% yield) as a beige solid.

Workup

  1. filtrationThe grey precipitate was filtered
  2. washwashed with water (10 mL)
  3. customdried for an hour at the pump
  4. custompurified by flash chromatography (0-10% MeOH in DCM, 24-g column)

Sources & evidence

ORD record
ord-b7feb1c416d14a4b8578c5b6d1774363
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

Loading…