Trimethyl orthoformate → 2-Chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinofuro[3,2-d]pyrimidine

HRID 2403359Notes

Reaction equation

HRID 2403359 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[O:10][C:9]([CH:11]=O)=[CH:8][C:6]=2[N:7]=1.[CH3:19][S:20]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)(=[O:22])=[O:21].C([O-])(=O)C.[Na+].C(OC)(OC)OC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[C:5]2[O:10][C:9]([CH2:11][N:26]3[CH2:27][CH2:28][N:23]([S:20]([CH3:19])(=[O:22])=[O:21])[CH2:24][CH2:25]3)=[CH:8][C:6]=2[N:7]=1

Participants

7

Reactant 5

HCID 9005Trimethyl orthoformateHCID 517045Sodium AcetateHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 568337422-Chloro-4-morpholinofuro[3,2-d]pyrimidine-6-carbaldehyde

Product 1

HCID 568337442-Chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinofuro[3,2-d]pyrimidineYield 69.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-Chloro-4-morpholinofuro[3,2-d]pyrimidine-6-carbaldehyde (65 mg, 1.0 eq) was dissolved in 1,2-dichloroethane (9.7 ml) and treated with hydrochloride salt of 1-methanesulfonylpiperazine (69 mg, 1.4 eq), sodium acetate (28 mg, 1.4 eq) and trimethyl orthoformate (0.27 ml, 10 eq). Reaction mixture was stirred at room temperature for 12 h. Sodium triacetoxyborohydride (62 mg, 1.2 eq) was added and reaction mixture was stirred at room temperature for 8 h. Reaction mixture was quenched with saturated aq. NaHCO3 and extracted with dichloromethane. The combined organic layers were dried (Na2SO4) and concentrated. The crude reaction mixture was purified by flash chromatography to yield 2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinofuro[3,2-d]pyrimidine (70 mg, 68%): MS (Q1) 416 (M)+.

Workup

  1. customReaction mixture
  2. customreaction mixture
  3. stirringwas stirred at room temperature for 8 h
  4. customReaction mixture
  5. customwas quenched with saturated aq. NaHCO3
  6. extractionextracted with dichloromethane
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude reaction mixture
  10. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-202be9ec03d041678e7bc95de70856bc
Source dataset
uspto-grants-2014_08
Patent number
US08802670B2

Reaction notes

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