Toluene ethanol → HCID 57967263, compound

HRID 1475541Notes

Reaction equation

HRID 1475541 reaction equation
[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[CH:17][CH:18]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].[F:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][C:46]([N:48]=[C:49]=[S:50])=[O:47])=[CH:41][CH:40]=1.C1(C)C=CC=CC=1.CCO>C1(C)C=CC=CC=1.CCO.CCOCC>[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:49]([NH:48][C:46](=[O:47])[CH2:45][C:42]4[CH:43]=[CH:44][C:39]([F:38])=[CH:40][CH:41]=4)=[S:50])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[CH:17][CH:18]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 21863594Toluene ethanolHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 579194724-[[2-[5-[[Boc(2-methoxyethyl)amino]methyl]-2-pyridyl]-7-thieno[3,2-b]pyridyl]oxy]-3-fluoroaniline

Product 1

HCID 57967263HCID 57967263, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a suspension of intermediate 13 (5.53 g, 10.55 mmol) in toluene (80 mL) and EtOH (80 mL) was added 2-(4-fluorophenyl)acetyl isothiocyanate (2) (3.09 g, 15.83 mmol) in a minimum of toluene-EtOH mixture (1:1). The reaction mixture was stirred at r.t. for 45 min then concentrated. The residue was purified by flash column chromatography (eluent EtOAc), followed by two triturations: first one in a mixture Et2O-EtOAc-hexanes and second one in Et2O, to afford intermediate 14 (4.68 g, 62% yield) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.49 (s, 1H), 11.84 (s, 1H), 8.55 (d, J=5.6 Hz, 1H), 8.51 (d, J=1.6 Hz, 1H), 8.34 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 8.04 (d, J=11.6 Hz, 1H), 7.79 (dd, J=8.2, 2.2 Hz, 1H), 7.55-7.54 (m, 2H), 7.38 (dd, J=8.6, 5.8 Hz, 2H), 7.18 (t, J=8.8 Hz, 2H), 6.69 (d, J=5.6 Hz, 1H), 4.48 (s, 2H), 3.84 (s, 2H), 3.43-3.34 (m, 4H), 3.23 (s, 3H), 1.44-1.34 (m, 9H). MS (m/z): 720.3 (M+H).

Workup

  1. concentrationthen concentrated
  2. customThe residue was purified by flash column chromatography (eluent EtOAc)

Sources & evidence

ORD record
ord-89d6b1e44a464b779248940375dfeea1
Source dataset
uspto-grants-2015_04
Patent number
US09018378B2

Reaction notes

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