3-Chloro-2,4-pentanedione → 5-Acetyl-2-amino-4-methylthiazole

HRID 1942986Notes

Reaction equation

HRID 1942986 reaction equation
S1C=CN=C1C1SC=CN=1.ClC1C=CC(OC)=C(NC2S[CH:21]=[C:22]([C:24]3[S:28][C:27]([NH:29]C(=O)C4C=CC=CC=4)=[N:26][C:25]=3[CH3:38])N=2)C=1.ClC(C(=O)C)C(=[O:45])C.NC(N)=S>C(O)C>[C:22]([C:24]1[S:28][C:27]([NH2:29])=[N:26][C:25]=1[CH3:38])(=[O:45])[CH3:21]

Participants

6

Reactant 4

HCID 743283-Chloro-2,4-pentanedioneHCID 819109HCID 819109, compoundHCID 1144671ST075396HCID 2723790Thiourea

Product 1

HCID 7208825-Acetyl-2-amino-4-methylthiazoleYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

An efficient route for the synthesis bithiazole analogs was developed as follows. Efforts began with a synthesis of N-(2-(5-chloro-2-methoxyphenylamino)-4′-methyl-4,5′-bithiazol-2′-yl)benzamide—the putative structure of “Corr-4” corrector 4. This work commenced by treating 3-chloropentane-2,4-dione with thiourea under reflux in absolute ethanol. 5-Acetyl-2-amino-4-methylthiazole (5) was obtained in 90% yield. Surprisingly, attempts to aminoacylate the 2-amino moiety in 5 with benzoyl chloride under various base, solvent and temperature conditions failed to deliver the desired intermediate N-(5-acetyl-4-methyl-thiazol-2-yl)-benzamide (6).

Sources & evidence

ORD record
ord-4040dd2679194fc0a60d88f694874df9
Source dataset
uspto-grants-2013_03
Patent number
US08389736B2

Reaction notes

Loading…