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

HRID 1972309Notes

Reaction equation

HRID 1972309 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[CH:10]=[C:9]([CH:11]=O)[S:8][C:6]=2[N:7]=1.[Cl-].[CH3:20][S:21]([N:24]1[CH2:29][CH2:28][NH2+:27][CH2:26][CH2:25]1)(=[O:23])=[O:22].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[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[CH:10]=[C:9]([CH2:11][N:27]3[CH2:28][CH2:29][N:24]([S:21]([CH3:20])(=[O:23])=[O:22])[CH2:25][CH2:26]3)[S:8][C:6]=2[N:7]=1

Participants

8

Reactant 6

HCID 9005Trimethyl orthoformateHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 162656121-Methanesulfonylpiperazine hydrochlorideHCID 568338442-Chloro-4-morpholinothieno[2,3-d]pyrimidine-6-carbaldehydeHCID 68731830HCID 68731830, compound

Product 1

HCID 568339462-Chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Scheme 7 shows the synthesis of 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[2,3-d]pyrimidin-4-yl)morpholine 20 by formylation of 4-(2-chlorothieno[2,3-d]pyrimidin-4-yl)morpholine 18 in THF at −78° C. with n-BuLi in hexanes (1.2 equiv.). The resulting slurry was allowed to warm up to −60° C., cooled to −78° C. and DMF (1.5 equiv.) was added slowly to afford 2-chloro-4-morpholinothieno[2,3-d]pyrimidine-6-carbaldehyde 19. To a suspension of 19, 4-(methylsulfonyl)piperazin-1-ium chloride 8 (alternatively named as 1-(methylsulfonyl)piperazine hydrochloride, 1.45 equiv.) and anhydrous sodium acetate in 1,2-dichloroethane was added trimethyl orthoformate (10 equiv.). The slurry was stirred at ambient temperature for at least 6 hours, then sodium triacetoxyborohydride was added and the reaction was stirred for 24 hours to give 20.

Workup

  1. stirringthe reaction was stirred for 24 hours

Sources & evidence

ORD record
ord-60c0bf008d574d01934186555036fd5c
Source dataset
uspto-grants-2013_04
Patent number
US08431694B1

Reaction notes

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