Trifluoroacetic acid → N-[(4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-10-yl]-5-chloro-3-methylpyridine-2-carboxamide

HRID 627740노트

반응식

HRID 627740 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:39])[C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:36][CH2:35][CH2:34][C@H:17]4[S:18](=[O:33])(=[O:32])[C:19]([CH3:31])([CH3:30])[C:20]([NH:22]C(=O)OC(C)(C)C)=[N:21][C@:16]4([CH3:37])[C:15]=3[CH:38]=2)=[O:9])=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:22][C:20]1[C:19]([CH3:31])([CH3:30])[S:18](=[O:32])(=[O:33])[C@@H:17]2[CH2:34][CH2:35][O:36][C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:5]4[C:4]([CH3:39])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=4)=[CH:38][C:15]=3[C@@:16]2([CH3:37])[N:21]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 90308596tert-butyl ((4aR,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate

생성물 1

HCID 90308598N-[(4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-10-yl]-5-chloro-3-methylpyridine-2-carboxamide수율 98%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of trans-isomer tert-butyl ((4aR,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (110 mg, 0.191 mmol) in DCM (2 ml) was treated with TFA (0.7 ml, 9.53 mmol) for 10 min at RT. The mixture was concentrated to dryness, redissolved in 0.5 ml of MeOH and neutralized with saturated solution NaHCO3. Precipitated material was extracted with ethyl acetate, organic extract was washed with water, brine, filtered through pad of celite and concentrated to afford N-((4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-chloro-3-methylpicolinamide (89 mg, 0.187 mmol, 98% yield). LC/MS (ESI+) m/z=477.

후처리

  1. concentrationThe mixture was concentrated to dryness
  2. dissolutionredissolved in 0.5 ml of MeOH and neutralized with saturated solution NaHCO3
  3. extractionPrecipitated material was extracted with ethyl acetate
  4. extractionorganic extract
  5. washwas washed with water, brine
  6. filtrationfiltered through pad of celite
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-a4875ba48d344dd1a8223ffd8a958582
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309263B2

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