m-Tolyl isocyanate → n-[4-(4-Aminothieno[3,2-c]pyridin-3-yl)-2-fluorophenyl]-n'-(3-methylphenyl)urea

HRID 17118

Reaction equation

HRID 17118 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C:13]([NH2:17])=[N:14][CH:15]=[CH:16][C:11]=3[S:10][CH:9]=2)=[CH:4][C:3]=1[F:18].[N:19]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=1)=[C:20]=[O:21]>ClCCl>[NH2:17][C:13]1[C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:20]([NH:19][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=4)=[O:21])=[C:3]([F:18])[CH:4]=3)=[CH:9][S:10][C:11]=2[CH:16]=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 69303m-Tolyl isocyanateHCID 184507073-(4-Amino-3-fluorophenyl)thieno[3,2-c]pyridin-4-amine

Product 1

HCID 18451344n-[4-(4-Aminothieno[3,2-c]pyridin-3-yl)-2-fluorophenyl]-n'-(3-methylphenyl)ureaYield 39.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of Example 1C (125 mg, 0.48 mmol) in dichloromethane (1 mL) was treated with 1-isocyanato-3-methylbenzene (0.065 mL, 0.5 mmol), stirred overnight at room temperature, and filtered. The filter cake was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a solvent gradient of 10% to 100% acetonitrile/10 mM aqueous ammonium acetate over 8 minutes (10 minute run time) at a flow rate of 40 mL/minute to provide 74 mg of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.30 (s, 3H), 5.48 (s, 2H), 6.83 (d, J=7.8 Hz, 1H), 7.18 (t, J=7.6 Hz, 1H), 7.22-7.29 (m, 2H), 7.28 (d, J=5.8 Hz, 1H), 7.32 (s, 1H), 7.38 (dd, J=12.0, 1.9 Hz, 1H), 7.50 (s, 1H), 7.84 (d, J=5.8 Hz, 1H), 8.31 (t, J=8.5 Hz, 1H), 8.70 (d, J=2.4 Hz, 1H), 9.06 (s, 1H); MS (ESI(+)) m/e 393.0 (M+H)+.

Workup

  1. filtrationfiltered
  2. customThe filter cake was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)
  3. customover 8 minutes
  4. custom(10 minute run time)

Sources & evidence

ORD record
ord-aee4070545bb4effb9f1695f16dee0b1
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Linked notes

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