(2R)-2,3-dihydro-1H-indol-2-ylmethanol → (R)-(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 1930557Notes

Reaction equation

HRID 1930557 reaction equation
FC(F)(F)S(O[C:7]1[C:8]2[CH2:29][N:28]([CH3:30])[CH2:27][CH2:26][C:9]=2[N:10]=[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:24]=[CH:23][N:22]=[C:21]3[CH3:25])=[CH:16][CH:15]=2)[N:12]=1)(=O)=O.[NH:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][C@@H:34]1[CH2:42][OH:43]>CS(C)=O>[CH3:30][N:28]1[CH2:27][CH2:26][C:9]2[N:10]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH:24]=[CH:23][N:22]=[C:21]4[CH3:25])=[CH:16][CH:15]=3)[N:12]=[C:7]([N:33]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH2:35][C@@H:34]3[CH2:42][OH:43])[C:8]=2[CH2:29]1

Participants

4

Reactant 2

HCID 6951187(2R)-2,3-dihydro-1H-indol-2-ylmethanolHCID 593337246-methyl-2-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl trifluoromethanesulfonate

Product 1

HCID 46200353(R)-(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)methanolYield 47.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

6-Methyl-2-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl trifluoromethanesulfonate (65 mg, 0.14 mmol, Example 9a) and (R)-indolin-2-ylmethanol (20.70 mg, 0.14 mmol) in DMSO (3 mL) were heated to 80° C. in a microwave reactor for 2 h. The reaction mixture was filtered and purified by preparative HPLC, yielding (R)-(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 (31.0 mg, 47.8%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-31f597c24e1745ccbadb9382d6e160b9
Source dataset
uspto-grants-2012_05
Patent number
US08188101B2

Reaction notes

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