Toluene → 1-{3-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea

HRID 2106093Notes

Reaction equation

HRID 2106093 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:32])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]3[CH2:31][CH:26]4[CH2:27][N:28]([CH3:30])[CH2:29][CH:25]4[CH2:24]3)=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1.C1(C)C=CC=CC=1.[C:40]1([CH2:46][C:47]([N:49]=[C:50]=[S:51])=[O:48])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:32][C:50]([NH:49][C:47](=[O:48])[CH2:46][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)=[S:51])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:22][CH:23]3[CH2:24][CH:25]4[CH2:29][N:28]([CH3:30])[CH2:27][CH:26]4[CH2:31]3)=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 12454157Phenylacetyl isothiocyanateHCID 578103153-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolin-4-yloxy]-phenylamine

Product 1

HCID 112735341-{3-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thioureaYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 3-fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolin-4-yloxy]-phenylamine (0.78 mg, 1.7 mmol, 1.0 eq.), toluene (10 ml), ethanol (10 ml) and phenyl-acetyl isothiocyanate (1.64 g, 9.2 mmol, 4.5 eq). The reaction mixture was stirred at room temperature overnight. After removal of the solvent the product was purified with a biotage system using an eluent EtOAc and 4% TEA (2 L) then EtOAc, 4% TEA, 1% MeOH (1 L). The solvent was removed to give 1-{3-fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea (0.5 g, 50% yield). 1H NMR (400 MHz, DMSO): 8.48 (d, 1H), 7.92 (dd, 1H), 7.53 (s, 1H), 7.40 (m, 4H), 7.33 (d, 2H), 7.23 (m, 2H), 6.54 (d, 2H), 6.39 (d, 1H), 4.21 (d, 2H), 4.02 (s, 3H), 3.81 (m, 3H), 2.87 (d, 2H), 2.73 (m, 4H), 2.53 (m, 1H), 2.27 (m, 2H), 2.01 (s, 3H), 1.36 (m, 2H); MS (EI) for C34H35FN4O4S: 615 (M+H+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. customAfter removal of the solvent the product
  3. customwas purified with a biotage system
  4. customThe solvent was removed

Sources & evidence

ORD record
ord-02118d1f0ad14f15bba602b4aaaff06a
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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