Phenylacetyl isothiocyanate → N-(3-Fluoro-4-(2-(4-(piperazin-1-ylmethyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenylcarbamothioyl)-2-phenylacetamide

HRID 1711119Notes

Reaction equation

HRID 1711119 reaction equation
[NH2:1][C:2]1[CH:37]=[CH:36][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:35]=[CH:34][C:19]([CH2:20][N:21]5[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]5)=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:38])[CH:3]=1.[C:39]1([CH2:45][C:46]([N:48]=[C:49]=[S:50])=[O:47])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>CCO.C1(C)C=CC=CC=1>[F:38][C:4]1[CH:3]=[C:2]([NH:1][C:49]([NH:48][C:46](=[O:47])[CH2:45][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)=[S:50])[CH:37]=[CH:36][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:17]=[CH:18][C:19]([CH2:20][N:21]4[CH2:22][CH2:23][NH:24][CH2:25][CH2:26]4)=[CH:34][CH:35]=3)[S:15][C:8]=12

Participants

4

Reactant 2

HCID 12454157Phenylacetyl isothiocyanateHCID 59457718tert-Butyl 4-(4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)benzyl)piperazine-1-carboxylate

Product 1

HCID 59457695N-(3-Fluoro-4-(2-(4-(piperazin-1-ylmethyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenylcarbamothioyl)-2-phenylacetamideYield 16%

Reagents, catalysts & solvents 1

HCID 21863594Toluene ethanolSolvent

Procedure

Compound 454 (0.3323 g, 0.62 mmol) was suspended in EtOH/toluene (3 mL/3 mL) at RT and stirred for 30 min. 2-Phenylacetyl isothiocyanate (0. 165 g, 0.93 mmol) was added and the reaction mixture was stirred at RT for 1 h, quenched with MeOH (2 mL) and concentrated to dryness. The residue was purified by flash chromatography (eluent 9/1/90 MeOH/NH4OH/DCM) to give compound 450 as a white solid (60 mg, 16% yield). 1H NMR δ(400 MHz, CD3CN): 8.51 (d, J=5.5 Hz, 1H), 7.99 (dd, J=2.5, 12.3 Hz, 1H), 7.84 (s, 1H), 7.82 (d, J=8.2 Hz, 2H), 7.32-7.53 (m, 9H), 6.62 (d, J=4.5 Hz, 1H), 3.81 (s, 2H), 3.54 (s, 2H), 2.30-2.53 (bs, 8H), 2.22 (s, 3H). LCMS: 613 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 h
  2. customquenched with MeOH (2 mL)
  3. concentrationconcentrated to dryness
  4. customThe residue was purified by flash chromatography (eluent 9/1/90 MeOH/NH4OH/DCM)

Sources & evidence

ORD record
ord-ab08e6fc11c74365a65ca1a61e74e507
Source dataset
uspto-grants-2010_09
Patent number
US07790729B2

Reaction notes

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