(S)-(+)-2-Indolinemethanol → (S)-(1-(6-methyl-2-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol

HRID 1930550Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@H:2]1[CH2:10][OH:11].FC(F)(F)S(O[C:18]1[C:19]2[CH2:40][N:39]([CH3:41])[CH2:38][CH2:37][C:20]=2[N:21]=[C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH:35]=[CH:34][N:33]=[C:32]3[CH3:36])=[CH:27][CH:26]=2)[N:23]=1)(=O)=O>CS(C)=O>[CH3:41][N:39]1[CH2:38][CH2:37][C:20]2[N:21]=[C:22]([NH:24][C:25]3[CH:26]=[CH:27][C:28]([N:31]4[CH:35]=[CH:34][N:33]=[C:32]4[CH3:36])=[CH:29][CH:30]=3)[N:23]=[C:18]([N:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3][C@H:2]3[CH2:10][OH:11])[C:19]=2[CH2:40]1

Participants

Conditions

Temperature: 80 °C

Procedure

(S)-Indolin-2-ylmethanol (25.5 mg, 0.17 mmol) was added to a solution of 6-methyl-2-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl trifluoromethanesulfonate (80 mg, 0.17 mmol, Example 9a) in DMSO (1 mL). The reaction was heated to 80° C. for 2 h. The solution was allowed to cool down, filtered and the product was purified on preparative HPLC to give (S)-(1-(6-methyl-2-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol (22.00 mg, 27.6%). MS (ESI+)/(ESI−) m/z 468/466

Workup

temperatureto cool down
filtrationfiltered
customthe product was purified on preparative HPLC

Sources & evidence

ORD record: ord-cf1dcdf03723445ebc77f66f0453c4bd
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188101B2

Reaction notes

Loading…