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

HRID 1910013Notes

Reaction equation

HRID 1910013 reaction equation
[ClH:1].[ClH:2].[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.N1[C:31]2[C:26](=[CH:27][C:28](C3C4C(N)=NC=NC=4N(C)C=3)=[CH:29][CH:30]=2)[CH2:25][CH2:24]1.CN(C([O:50]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O>[Cl:1][C:28]1[CH:27]=[C:26]([CH2:25][C:24]([N:3]2[C:11]3[C:6](=[CH:7][C:8]([C:12]4[C:20]5[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=5[N:14]([CH3:22])[CH:13]=4)=[CH:9][CH:10]=3)[CH2:5][CH2:4]2)=[O:50])[CH:31]=[C:30]([Cl:2])[CH:29]=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 668236055-{1-[(3,5-dichlorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 85.3%

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 (250 mg, 0.739 mmol), HATU (281 mg, 0.739 mmol), DIEA (0.516 mL, 2.96 mmol) was stirred at room temperature overnight. LCMS indicated good conversion, so the reaction mixture was poured into water (10 mL), whereupon a precipitate formed. The precipitate was filtered and washed with water (10 ml) and dried at the pump for an hour. The residual pale green solid was adsorbed onto silica and purified by flash chromatography (100% EtOAc to 10% MeOH in EtOAc, 12-g column) to afford 5-{1-[(3,5-dichlorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (285 mg, 85% yield) as a white solid. LC-MS (ES) m/z=452, 454 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.25 (t, J=8.3 Hz, 2H), 3.74 (s, 3H), 3.95 (s, 2H), 4.24 (t, J=8.5 Hz, 2H), 6.25-5.87 (br. s, 2H), 7.28-7.20 (m, 2H), 7.33 (s, 1H), 7.39 (d, J=1.8 Hz, 2H), 7.52 (d, J=1.8 Hz, 1H), 8.11 (d, J=8.1 Hz, 1H), 8.15 (s, 1H).

Workup

  1. customformed
  2. filtrationThe precipitate was filtered
  3. washwashed with water (10 ml)
  4. customdried at the pump for an hour
  5. custompurified by flash chromatography (100% EtOAc to 10% MeOH in EtOAc, 12-g column)

Sources & evidence

ORD record
ord-34de892b09e64c19b8d8406b7aa54044
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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