Dimethylformamide → 2-Chloro-4-morpholinothieno[2,3-d]pyrimidine-6-carbaldehyde

HRID 1972308Notes

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[CH:10]=[C:9]([CH2:11]N3CCN(S(C)(=O)=O)CC3)[S:8][C:6]=2[N:7]=1.ClC1N=C(N2CC[O:41]CC2)C2C=CSC=2N=1.[Li]CCCC.CN(C=O)C>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[CH:10]=[C:9]([CH:11]=[O:41])[S:8][C:6]=2[N:7]=1

Participants

Conditions

Temperature: -60 °C

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

temperaturecooled to −78° C.

Sources & evidence

ORD record: ord-14191d53c98d43d8b4b5c7ca73b262bc
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431694B1

Reaction notes

Loading…