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

HRID 1910011Notes

Reaction equation

HRID 1910011 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.[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32](O)=[O:33])[CH:27]=[C:28]([F:30])[CH:29]=1.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>>[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32]([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:33])[CH:27]=[C:28]([F:30])[CH:29]=1

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 1454243,5-Difluorophenylacetic acidHCID 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 dihydrochloride

Product 1

HCID 668236905-{1-[(3,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Procedure

A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (150 mg, 0.443 mmol), (3,5-difluorophenyl)acetic acid (76 mg, 0.443 mmol), HATU (169 mg, 0.443 mmol), DIEA (0.310 mL, 1.774 mmol) was stirred at room temperature overnight. LCMS indicated partial conversion, with a mixture of starting material, desired product and bis-acylated material, so the reaction mixture was poured into water (10 mL), and a precipitate formed. The precipitate was collected by filtration, and the residue was washed with water (10 mL), and dried at the pump for an hour. The beige solid was adsorbed onto silica, and purified by flash chromatography (0-10% methanol in DCM, 12-g column) to afford a pale yellow solid which showed presence of bis-acylated material. The product was adsorbed onto silica and purified by flash chromatography (100% EtOAc-10% MeOH in EtOAc, then 10% MeOH in DCM, 24-g column) to afford 5-{1-[(3,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (92 mg, 49.5% yield) as a white solid. LC-MS (ES) m/z=420 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.21-3.28 (m, 2H), 3.74 (s, 3H), 3.95 (s, 2H), 4.24 (t, J=8.34 Hz, 2H), 6.04 (br. s., 2H), 7.06 (d, J=6.57 Hz, 2H), 7.14 (t, J=9.60 Hz, 1H), 7.21-7.29 (m, 2H), 7.33 (s, 1H), 8.07-8.21 (m, 2H).

Sources & evidence

ORD record
ord-0d97f391aeb74df58ee81a061a116922
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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