9-Bromo-8-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamide → HCID 86693250, compound

HRID 575244Notes

Reaction equation

HRID 575244 reaction equation
Br[C:2]1[C:18]([F:19])=[CH:17][C:5]2[O:6][CH2:7][CH2:8][C:9]3[S:13][C:12]([C:14]([NH2:16])=[O:15])=[N:11][C:10]=3[C:4]=2[CH:3]=1.[CH3:20][Si:21]([CH3:37])([CH3:36])[CH2:22][CH2:23][O:24][CH2:25][N:26]1[CH:30]=[N:29][C:28](C(O)(C#C)C)=[N:27]1>>[F:19][C:18]1[C:2]([C:3]#[C:4][C:5]([OH:6])([C:30]2[N:26]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:20])([CH3:36])[CH3:37])[N:27]=[CH:28][N:29]=2)[CH3:17])=[CH:3][C:4]2[C:10]3[N:11]=[C:12]([C:14]([NH2:16])=[O:15])[S:13][C:9]=3[CH2:8][CH2:7][O:6][C:5]=2[CH:17]=1

Participants

3

Reactant 2

HCID 866930599-Bromo-8-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamideHCID 86693251HCID 86693251, compound

Product 1

HCID 86693250HCID 86693250, compound

Procedure

Similar to as described in General Procedure G, 9-bromo-8-fluoro-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide was reacted with and 2-(1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-1,2,4-triazol-3-yl)but-3-yn-2-ol to give 8-fluoro-9-(3-hydroxy-3-(1((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-5-yl)but-1-yn-1-yl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide. A solution of crude give 8-fluoro-9-(3-hydroxy-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-5-yl)but-1-yn-1-yl)-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide (150 mg, 0.28 mmol, 1.00 equiv) and hydrofluoric acid (2 mL) in CH3CN (4 mL) was stirred for 3 h at room temperature. The pH value of the solution was adjusted to 10 with saturated NaHCO3 (10 mL). The resulting solution was extracted with dichloromethane, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#pre-HPLC-006(waters)): Column, sunfire prep C18 19*150 mm 5 um; mobile phase, Water with 0.5% CF3COOH and CH3CN (10% CH3CN up to 45% in 12 min, up to 100% in 3 min, down to 10% in 2 min); Detector, UV 220/254 nm. 10 mg of product was obtained. This was treated by strong anion exchange resin (cleanert SAX-SPE). This resulted in 7.2 mg (6%) of the titled compound as an off-white solid.

Sources & evidence

ORD record
ord-3d496b8d0d1d44178d0cd9c7b85f8972
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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