Toluene ethanol → HCID 57967263, compound

HRID 1401312Notes

Reaction equation

HRID 1401312 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:37])[CH:3]=1.[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>[F:37][C:4]1[CH:3]=[C:2]([NH:1][C:49]([NH:48][C:46](=[O:47])[CH2:45][C:42]2[CH:43]=[CH:44][C:39]([F:38])=[CH:40][CH:41]=2)=[S:50])[CH:36]=[CH:35][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=3)[S:15][C:8]=12

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-1b9cb22bfcca403b84643c6671e5b9d0
Source dataset
uspto-grants-2014_12
Patent number
US08907091B2

Reaction notes

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