Thionyl Chloride → 2-[(2-Chloro-6-fluorophenyl)amino]-N-[6-(cyclopropylmethoxy)pyridin-3-yl]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxamide

HRID 1898393Notes

Reaction equation

HRID 1898393 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.[CH:31]1([CH2:34][O:35][C:36]2[N:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=2)[CH2:33][CH2:32]1.CCN(C(C)C)C(C)C>C1C=CC=CC=1.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]([CH3:23])([CH3:22])[O:21][C:17]=3[C:16]([C:24]([NH:42][C:39]3[CH:40]=[N:41][C:36]([O:35][CH2:34][CH:31]4[CH2:32][CH2:33]4)=[CH:37][CH:38]=3)=[O:26])=[CH:15][C:13]=2[N:14]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 284136536-(Cyclopropylmethoxy)pyridin-3-amineHCID 178422815HCID 178422815, compound

Product 1

HCID 1784227902-[(2-Chloro-6-fluorophenyl)amino]-N-[6-(cyclopropylmethoxy)pyridin-3-yl]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxamideYield 43.1%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 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, 0.200 g, 0.533 mmol), thionyl chloride (2.0 mL), 6-(cyclopropylmethoxy)pyridin-3-amine (Intermediate-42, 0.132 g, 0.799 mmol), THF (5.0 mL), DIPEA (2 mL) and benzene (5 mL). The obtained crude product was purified by column chromatography on basic alumina eluting with 2.0% MeOH: DCM to afford 0.120 g of the desired product. 1HNMR (DMSO-d6): δ 0.37-0.74 (m, 4H), 1.20 (m, 1H), 1.53 (s, 6H), 3.06 (s, 2H), 3.74 (d, J=6.9 Hz, 2H), 6.40 (d, J=6.6 Hz, 1H), 7.27-7.30 (m, 2H), 7.39-7.41 (m, 2H), 7.50 (d, J=9.6 Hz, 1H), 8.25 (s, 1H), 9.27 (s, 1H), 11.00 (s, 2H); MS [M+H]+: 522.17.

Workup

  1. customThe title compound was prepared
  2. customThe obtained crude product
  3. customwas purified by column chromatography on basic alumina eluting with 2.0% MeOH

Sources & evidence

ORD record
ord-82431807c2da40f7b5f552dc6732440b
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

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