Glutamic acid diethyl ester hydrochloride → HCID 46180058, compound
Reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.Cl.[CH2:11]([O:13][C:14](=[O:24])[C@H:15]([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[NH2:16])[CH3:12]>>[CH2:11]([O:13][C:14](=[O:24])[C@@H:15]([NH:16][C:7]([C:5]1[S:6][C:2]([Br:1])=[CH:3][CH:4]=1)=[O:9])[CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH3:12]Participants
Procedure
Target compounds AAG154353, AAG154360 and AAG154484 were synthesized as shown in Scheme 1. Commercially available pent-4-ynoic acid 1a or hex-5-ynoic acid 1b or hept-6-ynoic acid 1c (Scheme 1) was converted to the acid chlorides 2a-c and immediately reacted with diazomethane followed by 48% HBr to give the desired α-bromomethylketones 4a-c. Condensation of 2,4-diamino-6-hydroxypyrimidine with 4a-c at room temperature for 3 days afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 5a-c (51-74% yield). Compounds 6a-c were obtained by a Sonogashira coupling of 5a-c with (S)-2-[(5-bromo-thiophene-2-carbonyl)-amino]-pentanedioic acid diethyl ester 9. Hydrogenation and saponification of 6a-c afforded AAG154353, AAG154360 and AAG154484, respectively. Compound 9 (Scheme 1) was synthesized by coupling the commercially available 5-bromo-2-thiophene-carboxylic acid 8 and L-glutamate diethyl ester hydrochloride in 72% yield.
Sources & evidence
- ORD record
- ord-d4a95953ac0d407ab8131927d27625e1
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08252804B2
Reaction notes
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