Ethanol → HCID 117728077, compound

HRID 1772728Notes

Reaction equation

HRID 1772728 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([CH:33]=[C:34]([CH2:36][CH2:37][C:38]4[CH:47]=[CH:46][C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[N:39]=4)[N:35]=3)[C:10]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[C:23](=[O:24])[N:22](COCC[Si](C)(C)C)[N:21]=[CH:20]4)=[CH:15][CH:14]=3)=[CH:11][N:12]=2)[CH2:3][CH2:2]1.C(Cl)Cl.C(O)(C(F)(F)F)=O.O.CCO.CCN(C(C)C)C(C)C>CO.C(Cl)(Cl)Cl>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[C:8]3[N:9]([CH:33]=[C:34]([CH2:36][CH2:37][C:38]4[CH:47]=[CH:46][C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[N:39]=4)[N:35]=3)[C:10]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[C:23](=[O:24])[NH:22][N:21]=[CH:20]4)=[CH:15][CH:14]=3)=[CH:11][N:12]=2)[CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 18672661TFA dichloromethane waterHCID 123268525HCID 123268525, compound

Product 1

HCID 117728077HCID 117728077, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

Compound 82d (108 mg, 0.246 mmol) was treated with 5 mL of DCM-TFA-water (30:10:1) and stirred at room temperature for 1 h. EtOH (1 mL) was added and the mixture was concentrated to a pale yellow resin. The resulting material in DCM (10 mL) was treated with solid NaHCO3 (2 g), stirred 20 min, filtered, and concentrated to give a white solid which was purified by flash column chromatography on silica gel (0-25% MeOH-EtOAc) to afford a white solid. A portion (68.1 mg) of this material in MeOH (70 mL) and CHCl3 (20 mL) was treated with DIEA (229 μL, 1.32 mmol), refluxed for 2.5 h, and then concentrated to give a white solid which was purified by flash column chromatography on silica gel (0-25% MeOH-EtOAc) to afford the title compound 65 as a white solid. 1H-NMR (CDCl3-MeOH (3:1), 400 MHz): δ 8.15 (d, J=8.6 Hz, 1H), 8.02 (d, J=8.6 Hz, 1H), 7.92 (s, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.73 (ddd, J=8.4, 7.0, 1.5 Hz, 1H), 7.67-7.70 (m, 2H), 7.58-7.63 (m, 2H), 7.52-7.58 (m, 1H), 7.36-7.40 (m, 2H), 7.29 (s, 1H), 4.12-4.17 (m, 4H), 3.81-3.86 (m, 4H), 3.38-3.44 (m, 2H), 3.27-3.33 ppm (m, 2H). Mass spectrum (LCMS, ESI pos.): Calcd. for C29H26N8O2, 519.2 (M+H). found 519.0.

Workup

  1. concentrationthe mixture was concentrated to a pale yellow resin
  2. additionThe resulting material in DCM (10 mL) was treated with solid NaHCO3 (2 g)
  3. stirringstirred 20 min
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a white solid which
  7. customwas purified by flash column chromatography on silica gel (0-25% MeOH-EtOAc)
  8. customto afford a white solid
  9. temperaturerefluxed for 2.5 h
  10. concentrationconcentrated
  11. customto give a white solid which
  12. customwas purified by flash column chromatography on silica gel (0-25% MeOH-EtOAc)

Sources & evidence

ORD record
ord-a42bf428743f4f8eb09859c0cbb34114
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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