Acetic Acid → N-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,1-dimethylpiperidin-4-amine

HRID 390911Notes

Reaction equation

HRID 390911 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH:11]=O)=[C:8]([CH3:13])[C:6]=2[N:7]=1.CC(O)=O.[CH3:24][N:25]1[CH2:30][CH2:29][CH:28]([NH:31][CH3:32])[CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11][N:31]([CH3:32])[CH:28]3[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]3)=[C:8]([CH3:13])[C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5663231-Methyl-4-(methylamino)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 566485822-Chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

Product 1

HCID 86623525N-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,1-dimethylpiperidin-4-amineYield 88%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

2-Chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde (0.5 g) was dissolved in 10 mL of 1,2-DCE and 1.0 eq. AcOH and 1.3 eq. of 1-methyl-4-(methylamino)piperidine was added and the reaction was stirred 15 minutes followed by the addition of sodium triacetoxyborohydride. The reaction was stirred for 24 hours and product formation was confirmed by LCMS. The reaction was diluted with sat. NaHCO3, extracted with dichloromethane, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography (EtOAc/hexanes) to give 0.61 g N-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,1-dimethylpiperidin-4-amine (88% yield). MS (Q1) 411 (M)+.

Workup

  1. stirringThe reaction was stirred for 24 hours
  2. extractionextracted with dichloromethane
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-383910f1cc4f43e2bc9d1637fc13f538
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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