(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol → methyl 9-[(3R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-ynyl]-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:15][CH2:14][CH2:13][C:12]3[S:11][C:10]([C:16]([O:18][CH3:19])=[O:17])=[N:9][C:8]=3[C:6]=2[CH:7]=1.[CH3:20][C:21]1[O:25][N:24]=[C:23]([C@:26]([OH:30])([C:28]#[CH:29])[CH3:27])[CH:22]=1>O1CCOCC1>[OH:30][C@:26]([C:23]1[CH:22]=[C:21]([CH3:20])[O:25][N:24]=1)([CH3:27])[C:28]#[C:29][C:2]1[CH:3]=[CH:4][C:5]2[O:15][CH2:14][CH2:13][C:12]3[S:11][C:10]([C:16]([O:18][CH3:19])=[O:17])=[N:9][C:8]=3[C:6]=2[CH:7]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Methyl 9-bromo-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate (0.2 g) was reacted with (2R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol similar to as described in Procedure F but substituting CuI for ZnBr and Dioxane as the solvent to afford 70 mg of methyl 9-[(3R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-ynyl]-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate following reverse phase hplc purification. MS (Q1) 411.2 (M)+. Methyl 9-[(3R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-ynyl]-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate (70 mg) was saponified with LiOH in THF/water followed by similar to as described in Example 2 to afford 39.7 mg of 9-[(3R)-3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-ynyl]-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamide following reverse phase hplc purification. MS (Q1) 396 (M)+. 1H NMR (400 MHz, DMSO) δ 8.60 (d, J=2.1 Hz, 1H), 8.42 (s, 1H), 7.85 (s, 1H), 7.31 (dd, J=8.3, 2.2 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H), 6.46 (s, 1H), 6.36 (s, 1H), 4.35 (t, J=4.9 Hz, 2H), 3.41 (t, J=4.9 Hz, 2H), 2.41 (s, 3H), 1.81 (s, 3H).
Sources & evidence
- ORD record
- ord-136793fd4a6940c2963038b5afff6c22
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Reaction notes
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