Tetrabutylammonium Fluoride → HCID 86722381, compound

HRID 718784Notes

Reaction equation

HRID 718784 reaction equation
[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

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 86722365HCID 86722365, compoundHCID 86722382HCID 86722382, compound

Product 1

HCID 86722381HCID 86722381, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-ef57da531149465d878230bcd89823b2
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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