2-Chloro-4-(morpholin-4-yl)thieno(3,2-d)pyrimidine → 2-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

HRID 1972305Notes

Reaction equation

HRID 1972305 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH2:11]N3CCN(S(C)(=O)=O)CC3)=[CH:8][C:6]=2[N:7]=1.ClC1N=C(N2CC[O:41]CC2)C2SC=CC=2N=1.[Li]CCCC>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH:11]=[O:41])=[CH:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 202849712-Chloro-4-(morpholin-4-yl)thieno(3,2-d)pyrimidineHCID 236508374-(2-Chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholineHCID 178418339Butyllithium

Product 1

HCID 457899852-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Scheme 4 shows the synthesis of 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 9 starting with formylation at the 7-position of 4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 4 (1.0 equiv.) in THF with n-BuLi in hexanes to give 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 5 after acidification. Reductive amination of aldehyde 5 was accomplished with 4-(methylsulfonyl)piperazin-1-ium chloride 8 and sodium acetate (anhydrous powder) in 1,2-dichloroethane. Trimethyl orthoformate was added and stirred for 6 hours, followed by the addition of sodium triacetoxyborohydride to give 9.

Sources & evidence

ORD record
ord-539aa0f866714a4e96e0d6f03dc30fc3
Source dataset
uspto-grants-2013_04
Patent number
US08431694B1

Reaction notes

Loading…