2-Amino-4-methylthiazole → HCID 86607596, compound
Reaction equation
[Al](C)(C)C.C(O[C:8]([C:10]1[C:15]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:14][CH:13]=[C:12]([C:24](C)(C)[O:25][SiH2]C(C)(C)C)[N:11]=1)=[O:9])C.[NH2:33][C:34]1[S:35][CH:36]=[C:37]([CH3:39])[N:38]=1>>[C:20]([O:19][C:17](=[O:18])[NH:16][C:15]1[C:10]([C:8](=[O:9])[NH:33][C:34]2[S:35][CH:36]=[C:37]([CH3:39])[N:38]=2)=[N:11][C:12]([CH2:24][OH:25])=[CH:13][CH:14]=1)([CH3:21])([CH3:22])[CH3:23]Participants
Procedure
The Al(Me)3-catalyzed reaction of 0.53 g (1.29 mmol) of 3-tert-Butoxycarbonylamino-6-(tert-butyl-dimethyl-silanyloxymethyl)-pyridine-2-carboxylic acid ethyl ester and 2-amino-4-methyl thiazole in accordance with the general method of Example 78, step 2 yielded 0.58 g of crude [6-Hydroxymethyl-2-(4-methyl-thiazol-2-ylcarbamoyl)-pyridin-3-yl]-carbamic acid tert-butyl ester (which also contains 2-amino-4-methyl thiazole) as a dark brown oil, MS (ISP): m/e=365.1 (M+H+). This crude material was dissolved in 4 ml of methylene chloride and 2.4 ml of trifluoroacetic acid. The solution was stirred overnight at room temperature. The pH of the solution was adjusted to 8 by addition of saturated sodium carbonate solution and extracted three times with methylene chloride. The combined organic phases were dried over magnesium sulfate and concentrated to yield 0.47 g of 3-Amino-6-hydroxymethyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide as a dark brown oil (containing 2-amino-4-methyl thiazole), MS (ISP): m/e=265.3 (M+H+). The crude material was reprotected with tert-butyldimethylchlorosilane/imidazole according to the general procedure described in step 4 to yield, after extraction and purification, 88 mg (0.23 mmol, 13%) of the pure title compound as a light yellow solid, MS (ISP): m/e=379.3 (M+H+).
Sources & evidence
- ORD record
- ord-e6fd3a073ba44c979c7bef62d8ada5fe
- Source dataset
- uspto-grants-2008_08
- Patent number
- US07414060B2
Reaction notes
Loading…