Tetrabutylammonium Fluoride → HCID 86722381, 화합물

HRID 718784노트

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HRID 718784 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@@H:20]5[CH2:25][C@@:24]([O:30][Si](CC)(CC)CC)([C:26]([F:29])([F:28])[F:27])[CH2:23][CH2:22][C@@:21]5([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(O[C@@]1(C(F)(F)F)C[C@H]2CCCC3C(=CC4C=NN(C5C=CC(F)=CC=5)C=4C=3)[C@]2(CN2CCCS2(=O)=O)CC1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@H:20]5[CH2:25][C@:24]([OH:30])([C:26]([F:27])([F:28])[F:29])[CH2:23][CH2:22][C@:21]5([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@@H:20]5[CH2:25][C@@:24]([OH:30])([C:26]([F:27])([F:28])[F:29])[CH2:23][CH2:22][C@@:21]5([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 2724141Tetrabutylammonium FluorideHCID 86722365HCID 86722365, 화합물HCID 86722382HCID 86722382, 화합물

생성물 1

HCID 86722381HCID 86722381, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A solution of N-(((3R,4aR,12bS)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)acetamide compound with N-(43 S,4aS,12bR)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)acetamide (35, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rg=TES) (195 mg, 0.32 mmol) in DCM (5 mL) was treated with TBAF (1M solution in THF, 0.32 mL, 0.32 mmol) at rt for about 30 min. The reaction was diluted with DCM (10 mL), washed with water (3×5 mL), dried over Na2SO4, filtered and concentrated to solids under reduced pressure. The residue was triturated in EtOAc (˜2 mL), filtered, rinsed with heptane and dried under vacuum to yield N-(((3R,4aR,12bS)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)acetamide; compound with N-(((3S,4aS,12bR)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)acetamide (36, R1=4-Fluorophenyl, R3=Trifluoromethyl, R4=Acetyl) as a white solid (125 mg, 72%); LC/MS, method 4, Rt=1.55 min, MS m/z 490 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.25 (d, J=0.7 Hz, 1H), 7.81-7.73 (m, 3H), 7.55 (s, 1H), 7.44-7.35 (m, 2H), 7.07 (t, J=5.9 Hz, 1H), 5.88 (s, 1H), 4.00-3.91 (m, 1H), 3.65-3.56 (m, 1H), 3.42-3.31 (m, 1H), 3.00-2.90 (m, 1H), 2.13-1.94 (m, 3H), 1.95-1.77 (m, 4H), 1.71-1.61 (m, 3H), 1.59 (s, 3H), 1.45-1.32 (m, 1H).

후처리

  1. washwashed with water (3×5 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated to solids under reduced pressure
  5. customThe residue was triturated in EtOAc (˜2 mL)
  6. filtrationfiltered
  7. washrinsed with heptane
  8. customdried under vacuum

출처 및 근거

ORD 기록
ord-ef57da531149465d878230bcd89823b2
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193744B2

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