Tetrabutylammonium Fluoride → HCID 56644066, compound

HRID 921980Notes

Reaction equation

HRID 921980 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6](=[O:60])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([S:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21](=[O:59])[NH:22][C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:25][C:24]=3[C:35]([C:37]3[N:38](S(C4C=CC=CC=4)(=O)=O)[C:39]4[C:44]([CH:45]=3)=[CH:43][CH:42]=[C:41]([C:46]([F:49])([F:48])[F:47])[CH:40]=4)=[O:36])[CH:16]=2)[CH:8]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CO.C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6](=[O:60])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([S:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21](=[O:59])[NH:22][C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)=[CH:25][C:24]=3[C:35]([C:37]3[NH:38][C:39]4[C:44]([CH:45]=3)=[CH:43][CH:42]=[C:41]([C:46]([F:48])([F:49])[F:47])[CH:40]=4)=[O:36])[CH:16]=2)[CH:8]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 66587586HCID 66587586, compound

Product 1

HCID 56644066HCID 56644066, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Into a 50-mL round-bottom flask was placed a solution of N-(2-methoxyethyl)-3-(3-(2-(1-(phenylsulfonyl)-6-(trifluoromethyl)-1H-indole-2-carbonyl)-4-(piperidin-1-yl)phenylcarbamoyl)benzylthio)-benzamide (200 mg, 0.23 mmol, 1.00 equiv) in methanol (3.5 mL), and 3.5 mL of a 1.0 N solution of tetrabutylammonium fluoride in THF. The resulting solution was stirred overnight at 80° C. The resulting mixture was concentrated under vacuum. The residue was dissolved in 50 mL of ethyl acetate. The resulting mixture was washed with 3×20 mL of water. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (100 mg) was purified by HPLC with the following conditions (Waters 2767-3): Column, SunFire Prep C18, 19×150 mm Sum; mobile phase, water with 0.05% TFA and CH3CN (gradient of 49% to 61% CH3CN over 6 min); Detector, Waters 2545 UV Detector 254 and 270 nm. This resulted in 38.1 mg (17%) of N-(2-methoxyethyl)-3-(3-(4-(piperidin-1-yl)-2-(6-(trifluoromethyl)-1H-indole-2-carbonyl)-phenylcarbamoyl)benzylthio)benzamide as a orange solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.38 (d, J=9 Hz, 1H), 8.01 (d, J=3 Hz, 1H), 7.91-7.87 (m, 2H), 7.78-7.73 (m, 4H), 7.62-7.59 (m, 1H), 7.53-7.51 (m, 1H), 7.47-7.26 (m, 5H), 4.23 (s, 2H), 3.62-3.57 (m, 4H), 3.53 (s, 3H), 3.35-3.34 (m, 2H), 1.98-1.96 (m, 4H), 1.79-1.77 (m, 2H). MS (ES, m/z): 715 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. dissolutionThe residue was dissolved in 50 mL of ethyl acetate
  4. washThe resulting mixture was washed with 3×20 mL of water
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product (100 mg) was purified by HPLC with the following conditions (Waters 2767-3)
  8. customwith 0.05% TFA and CH3CN (gradient of 49% to 61% CH3CN over 6 min)
  9. customThis resulted in 38.1 mg (17%) of N-(2-methoxyethyl)-3-(3-(4-(piperidin-1-yl)-2-(6-(trifluoromethyl)-1H-indole-2-carbonyl)-phenylcarbamoyl)benzylthio)benzamide as a orange solid

Sources & evidence

ORD record
ord-29377619d3cd450488042e4154825ce7
Source dataset
uspto-grants-2016_03
Patent number
US09278102B2

Reaction notes

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