Tetrabutylammonium Fluoride → HCID 86722381、化合物

HRID 718784ノート

反応式

HRID 718784 の反応式
[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

参加物

5

反応物 3

HCID 2724141Tetrabutylammonium FluorideHCID 86722365HCID 86722365、化合物HCID 86722382HCID 86722382、化合物

生成物 1

HCID 86722381HCID 86722381、化合物

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-ef57da531149465d878230bcd89823b2
出典データセット
uspto-grants-2015_11
特許番号
US09193744B2

反応ノート

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