Thionyl Chloride → 2-[(2-Chloro-6-fluorophenyl)amino]-7,7-dimethyl-N-[2-methyl-4-(trifluoromethyl)phenyl]-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxamide

HRID 1898382Notes

Reaction equation

HRID 1898382 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:11][C:12]2[C:18]3[CH2:19][C:20]([CH3:23])([CH3:22])[O:21][C:17]=3[C:16]([C:24]([OH:26])=O)=[CH:15][C:13]=2[N:14]=1.S(Cl)(Cl)=O.[CH3:31][C:32]1[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:33]=1[NH2:34].CCN(C(C)C)C(C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:11][C:12]2[C:18]3[CH2:19][C:20]([CH3:22])([CH3:23])[O:21][C:17]=3[C:16]([C:24]([NH:34][C:33]3[CH:35]=[CH:36][C:37]([C:39]([F:40])([F:41])[F:42])=[CH:38][C:32]=3[CH3:31])=[O:26])=[CH:15][C:13]=2[N:14]=1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 137504374-Amino-3-methylbenzotrifluorideHCID 178422815HCID 178422815, compound

Product 1

HCID 1784260402-[(2-Chloro-6-fluorophenyl)amino]-7,7-dimethyl-N-[2-methyl-4-(trifluoromethyl)phenyl]-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxamideYield 10.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared by following the procedure described for Example-108 using 2-[(2-chloro-6-fluorophenyl)amino]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxylic acid (Intermediate-15, 0.100 g, 0.266 mmol), thionyl chloride (2.0 mL), 2-methyl-4-(trifluoromethyl)aniline (0.070 g, 0.400 mmol), THF (10.0 mL) and DIPEA (2 mL). The obtained crude product was purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH:DCM to afford 0.015 g of the desired product. 1HNMR (DMSO-d6): δ 1.56 (s, 6H), 2.41 (s, 3H), 3.12 (s, 2H), 7.32-7.39 (m, 3H), 7.57 (d, J=7.2 Hz, 1H), 7.63 (s, 1H), 8.63 (d, J=8.4 Hz, 2H), 9.31 (s, 1H), 9.84 (s, 1H), 11.18 (s, 1H); MS [M−H]−: 531.41.

Workup

  1. customThe title compound was prepared
  2. customThe obtained crude product
  3. customwas purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH

Sources & evidence

ORD record
ord-eacd9627b35a49bf8154deb0bd2ae792
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

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