tert-Butyl bromoacetate → HCID 86594358, compound
Reaction equation
[CH:1]1([CH2:6][CH:7]([C:16]2[CH:17]=[N:18][C:19]([SH:22])=[CH:20][CH:21]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>>[CH:1]1([CH2:6][CH:7]([C:16]2[CH:21]=[CH:20][C:19]([S:22][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:18][CH:17]=2)[C:8](=[O:9])[NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1Participants
Procedure
3-Cyclopentyl-2-(6-mercaptopyridin-3-yl)-N-thiazol-2-ylpropionamide (EXAMPLE 66, 94 mg, 283 μmol) was alkylated with tert-butyl bromoacetate (55 mg, 283 μmol), using the procedure described in EXAMPLE 72, to give tert-butyl {5-[2-cyclopentyl-1-(thiazol-2-ylcarbamoyl)ethyl]pyridin-2-ylsulfanyl}acetate: m/z (ES+)=448.3 [M+H]+. Step 2: Oxidation of this thioether, employing the protocol described in EXAMPLE 35, provided tert-butyl {5-[2-cyclopentyl-1-(thiazol-2-ylcarbamoyl)-ethyl]pyridine-2-sulfonyl}acetate: δH (CDCl3): 1.05-1.20 (m, 2H), 1.25 (s, 9H), 1.45-1.85 (m, 7H), 1.90-2.00 (m, 1H), 2.30-2.40 (m, 1H), 3.90-4.00 (m, 1H), 4.30-4.45 (m, 2H), 7.10 (d, 1H), 7.55 (d, 1H), 8.05 (d, 1H), 8.10 (dd, 1H), 8.70 (d, 1H). Step 3: A solution of this compound (48 mg, 100 μmol) in CH2Cl2-TFA (1:3, 4 mL) was stirred at 20° C. for 2 h. Ths solvents were evaporated, then the remainder was treated with saturated aqueous NaHCO3 (5 mL). The resulting solution was acidified with 2M HCl to pH 2, then the mixture was extracted with EtOAc (10 mL+5 mL). The organic layer was concentrated and chromatographed (MeOH—CH2Cl2-AcOH, 2:18:1) to furnish the title compound: RTA=3.37 min; m/z (ES+)=424.1 [M+H]+.
Sources & evidence
- ORD record
- ord-711c87adf77a4d0f956b2a4ed7eb2065
- Source dataset
- uspto-grants-2007_08
- Patent number
- US07262196B2
Reaction notes
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