Acetic Acid → (S)-4-(5-(3-fluoro-4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine

HRID 1478588Notes

Reaction equation

HRID 1478588 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][C:13]([N:16]3[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][N:23]4[C:27]5=[N:28][C:29]([C:32]6[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=6)=[CH:30][N:31]=[C:26]5[N:25]=[N:24]4)[CH2:17]3)=[N:14][CH:15]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.CC(O)=O.[CH3:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.C([O-])([O-])=O.[K+].[K+]>ClCCl>[F:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][C:13]([N:16]3[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][N:23]4[C:27]5=[N:28][C:29]([C:32]6[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=6)=[CH:30][N:31]=[C:26]5[N:25]=[N:24]4)[CH2:17]3)=[N:14][CH:15]=2)[CH:7]=[CH:6][C:3]=1[CH2:4][N:46]1[CH2:47][CH2:48][N:43]([CH3:42])[CH2:44][CH2:45]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 118364829(S)-2-fluoro-4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)-methyl)morpholino)pyrimidin-5-yl)benzaldehyde

Product 1

HCID 118364826(S)-4-(5-(3-fluoro-4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholineYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-fluoro-4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)-methyl)morpholino)pyrimidin-5-yl)benzaldehyde (41 mg, 0.09 mmol) was dissolved in dichloromethane (3 mL), and then AcOH (0.006 mL, 0.10 mmol) and 1-methylpiperazine (0.02 mL, 0.17 mmol) were added. The mixture was stirred at room temperature for 30 minutes, and then NaBH(OAC)3 (28 mg, 0.13 mmol) was added, followed by stirring at room temperature for 13 hours. When the reaction was completed, the reaction mixture was adjusted to pH 8 with 5% K2CO3, followed by extraction with dichloromethane and water two times or more. The organic layer was extracted with ethyl acetate and water, and the extra water was removed by sodium sulfate, followed by concentration under reduced pressure. PLC using 10% dichloromethane/methanol gave (S)-4-(5-(3-fluoro-4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine (20 mg, 0.034 mmol) with a yield of 46%.

Workup

  1. stirringby stirring at room temperature for 13 hours
  2. extractionfollowed by extraction with dichloromethane and water two times
  3. extractionThe organic layer was extracted with ethyl acetate and water
  4. customthe extra water was removed by sodium sulfate
  5. concentrationfollowed by concentration under reduced pressure

Sources & evidence

ORD record
ord-f7630457de22433aa6dd735aa6786b1c
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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