Ethanol → HCID 136310633, compound

HRID 1772734Notes

Reaction equation

HRID 1772734 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)[CH:21]=[N: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>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][CH:21]=[N:20]4)=[CH:15][CH:14]=3)=[CH:11][N:12]=2)[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 18672661TFA dichloromethane waterHCID 123984127HCID 123984127, compound

Product 1

HCID 136310633HCID 136310633, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Compound 84e (89.8 mg, 0.138 mmol) was treated with 5 mL of DCM-TFA-water (30:10:1) and stirred at rt for 14 h. EtOH (1 mL) was added and the mixture was concentrated to a yellow resin (112 mg). The resulting material was taken up in MeOH (20 mL) and CHCl3 (10 mL), treated with DIEA (241 μL, 1.38 mmol), refluxed for 2 h, and then concentrated to give a beige solid. The solid was then purified by flash column chromatography on silica gel (100% EtOAc, followed by 0-30% MeOH-EtOAc) to afford a beige solid that was washed with MeOH (1.5 mL) and dried to give compound 21 as an off-white solid. 1H-NMR (CDCl3—CD3OD (1:1), 400 MHz): δ 8.19 (d, J=8.6 Hz, 1H), 8.05 (d, J=8.6 Hz, 2H), 8.00 (d, J=8.1 Hz, 1H), 7.87 (d, J=9.1 Hz, 1H), 7.81 (s, 1H), 7.72-7.77 (m, 1H), 7.54-7.59 (m, 1H), 7.52 (d, J=9.1 Hz, 2H), 7.38-7.42 (m, 2H), 7.28 (s, 1H), 4.06-4.10 (m, 4H), 3.81-3.85 (m, 4H), 3.38-3.44 (m, 2H), 3.29-3.33 (m, 2H); Mass spectrum (LCMS, ESI pos.): Calcd. for C29H26N8O2, 519.2 (M+H). found 519.4.

Workup

  1. concentrationthe mixture was concentrated to a yellow resin (112 mg)
  2. temperaturerefluxed for 2 h
  3. concentrationconcentrated
  4. customto give a beige solid
  5. customThe solid was then purified by flash column chromatography on silica gel (100% EtOAc, followed by 0-30% MeOH-EtOAc)
  6. customto afford a beige solid
  7. washthat was washed with MeOH (1.5 mL)
  8. customdried

Sources & evidence

ORD record
ord-0d729e1bb5d9414aa7b360891d3a543e
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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