1-Butanol → 2-{4-[2-Hydroxy-3-(N,N-dimethylamino)propoxy]anilino}-4-(indolin-1-yl)pyrimidine

HRID 2083895Notes

Reaction equation

Cl.[OH:2][CH:3]([CH2:13][N:14]([CH3:16])[CH3:15])[CH2:4][O:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1.Cl[C:18]1[N:23]=[C:22]([N:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26][CH2:25]2)[CH:21]=[CH:20][N:19]=1.C(O)CCC>CO>[OH:2][CH:3]([CH2:13][N:14]([CH3:16])[CH3:15])[CH2:4][O:5][C:6]1[CH:12]=[CH:11][C:9]([NH:10][C:18]2[N:23]=[C:22]([N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:26][CH2:25]3)[CH:21]=[CH:20][N:19]=2)=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A hot solution of 4-[2-hydroxy-3-(N,N-dimethylamino)propoxy]aniline hydrochloride (Method 1, 219 mg, 0.77 mmol) in methanol (2 ml) was added to a solution of 2-chloro-4-(indolin-1-yl)pyrimidine (Method 3, 200 mg, 0.86 mmol) in ii-butanol (20 ml). The mixture was heated at 100° C. for 18 hours and silica (1 g) was added. Volatile material was removed by evaporation and the residue was purified by column chromatography, eluting with 0-5% 2.0M methanolic ammonia solution in DCM, to give the product as a colourless solid (201 mg, 61%). NMR: 2.19 (s, 6H), 2.21-2.3 (m, 1H), 2.3-2.4 (m, 1H), 3.1-3.25 (m, 2H), 3.8-4.1 (m, 5H), 5.75 (m, 1H), 6.2 (m, 2H), 6.8-6.9 (m, 3H), 7.0-7.1 (m, 1H), 7.15-7.25 (m, 1H), 7.5-7.6 (m, 2H), 8.05-8.1 (m, 1H), 8.3-8.4 (m, 1H), 8.95 (s, 1H); MS (MH+): 406.5.

Workup

additionsilica (1 g) was added
customVolatile material was removed by evaporation
customthe residue was purified by column chromatography
washeluting with 0-5% 2.0M methanolic ammonia solution in DCM

Sources & evidence

ORD record: ord-3c1dfe304b064762a931b827db079c22
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06716831B1

Reaction notes

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