Triethylamine → 4-(4-(7-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzyl)-N-methylpiperazine-1-carboxamide

HRID 1711120Notes

Reaction equation

HRID 1711120 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:31][C:32]([NH:34][C:35](=[O:43])[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[S:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)[S:17][C:10]=12.CCN(CC)CC.[N:51]([CH3:54])=[C:52]=[O:53]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([NH:31][C:32]([NH:34][C:35](=[O:43])[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[S:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][N:28]([C:52]([NH:51][CH3:54])=[O:53])[CH2:27][CH2:26]4)=[CH:22][CH:23]=3)[S:17][C:10]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12228Methyl IsocyanateHCID 59457695N-(3-Fluoro-4-(2-(4-(piperazin-1-ylmethyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenylcarbamothioyl)-2-phenylacetamide

Product 1

HCID 167179204-(4-(7-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzyl)-N-methylpiperazine-1-carboxamideYield 39.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Compound 450 (0.367 g, 0.60 mmol) was dissolved in dichloromethane (2 mL) at RT and then Et3N (0.25 mL, 1.803 mmol) was added. The reaction mixture was cooled to 0° C., treated with isocyanatomethane (0. 16 mL, 3.43 mmol) and stirred for 10 min at 0° C. The reaction mixture was then warmed to RT over a 30 min period, and then was quenched with MeOH. It was then concentrated to dryness and the residue was purified by flash chromatography (eluent 9/1/10 MeOH/NH4Cl/DCM) to give title compound 455 as a pale yellow solid (0.16 g, 39% yield). 1H NMR δ (400 MHz, DMSO-d6): 12.48 (s, 1H), 11.83 (s, 1 H), 8.51 (dd, J=1.2, 5.5 Hz, 1H), 8.01 (m, 2H), 7.84 (m, 2H), 7.53 (m, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.23-7.38 (m, 5H) 6.65 (dd, J=0.8, 5.5 Hz, 1H), 6.39 (q, J=4.2 Hz, 1 H), 3.81 (s, 2 H), 3.51 (s, 2H), 3.25 (m, 4H), 2.53 (d, J=4.3 Hz, 3H), 2.31 (m, 4H). LCMS: 669 (M+H)+.

Workup

  1. temperatureThe reaction mixture was then warmed to RT over a 30 min period
  2. customwas quenched with MeOH
  3. concentrationIt was then concentrated to dryness
  4. customthe residue was purified by flash chromatography (eluent 9/1/10 MeOH/NH4Cl/DCM)

Sources & evidence

ORD record
ord-b1fc1e9928594df1926c2196b60f9dc1
Source dataset
uspto-grants-2010_09
Patent number
US07790729B2

Reaction notes

Loading…