Acetic Acid → (S)-(1-(6-methyl-2-(methyl(4-(2-methyl-1H-imidazol-1-yl)phenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol

HRID 1930641Notes

Reaction equation

HRID 1930641 reaction equation
[CH3:1][C:2]1[N:3]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:15]=[C:16]([N:24]4[C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[CH2:26][C@H:25]4CO)[C:17]4[CH2:23][NH:22][CH2:21]C[C:18]=4[N:19]=3)=[CH:9][CH:8]=2)[CH:4]=[CH:5][N:6]=1.[C:35](O)(=O)[CH3:36].[CH2:39]=[O:40].[C:41]([BH3-])#N.[Na+]>CO>[CH3:21][N:22]1[CH2:36][CH2:35][C:18]2[N:19]=[C:14]([N:13]([CH3:41])[C:10]3[CH:9]=[CH:8][C:7]([N:3]4[CH:4]=[CH:5][N:6]=[C:2]4[CH3:1])=[CH:12][CH:11]=3)[N:15]=[C:16]([N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:26][C@H:25]3[CH2:39][OH:40])[C:17]=2[CH2:23]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59333741(S)-(1-(2-(4-(2-Methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol

Product 1

HCID 46199433(S)-(1-(6-methyl-2-(methyl(4-(2-methyl-1H-imidazol-1-yl)phenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanolYield 27.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(S)-(1-(2-(4-(2-Methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol (49 mg, 0.11 mmol) was dissolved in methanol (3 mL). Acetic acid (6.18 μL, 0.11 mmol) was added followed by formaldehyde (0.016 mL, 0.22 mmol). The reaction mixture was allowed to stirred at room temperature for 15 minutes and sodium cyanoborohydride (13.58 mg, 0.22 mmol) was added. After 1 h the solvent was evaporated and the crude dissolved in few drops of methanol, filtered and purified by preparative HPLC to give (S)-(1-(6-methyl-2-(methyl(4-(2-methyl-1H-imidazol-1-yl)phenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol (14.80 mg, 26.2%) and (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 (4.60 mg, 8.07%) were obtained as acetate salt.

Workup

  1. customAfter 1 h the solvent was evaporated
  2. dissolutionthe crude dissolved in few drops of methanol
  3. filtrationfiltered
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-02a6b51ab5cd46479b95c5a24a549bba
Source dataset
uspto-grants-2012_05
Patent number
US08188101B2

Reaction notes

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