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

HRID 1365259Notes

Reaction equation

HRID 1365259 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 68%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-Chloro-4-morpholinofuro[3,2-d]pyrimidine-6-carbaldehyde 39 prepared following Example 20 (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 r.t. for 12 h. Sodium triacetoxyborohydride (62 mg, 1.2 eq) was added and reaction mixture was stirred at r.t. 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 r.t. 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-144e10372ad54bf8998a73dcb2908412
Source dataset
uspto-grants-2011_02
Patent number
US07888352B2

Reaction notes

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