Tetrahydrofuran → HCID 178447325, compound

HRID 410116Notes

Reaction equation

HRID 410116 reaction equation
[F:1][C:2]([F:27])([F:26])[C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:25])[C:11]2[CH:16]=[C:15]([NH2:17])[C:14]([N+:18]([O-])=O)=[CH:13][C:12]=2[O:21][CH:22]([F:24])[F:23])[CH2:5][CH2:4]1.C1COCC1.[Cl:33][C:34]1[C:47]([N:48]=[C:49]=S)=[C:46]([Cl:51])[CH:45]=[CH:44][C:35]=1[CH2:36][NH:37][C:38](=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40].CC(C)N=C=NC(C)C>CC#N.[Pd]>[F:1][C:2]([F:27])([F:26])[C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:11]2[C:12]([O:21][CH:22]([F:24])[F:23])=[CH:13][C:14]3[NH:18][C:49]([NH:48][C:47]4[C:46]([Cl:51])=[CH:45][CH:44]=[C:35]([CH2:36][NH:37][C:38](=[O:43])[C:39]([CH3:40])([CH3:41])[CH3:42])[C:34]=4[Cl:33])=[N:17][C:15]=3[CH:16]=2)=[O:25])[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 12734DiisopropylcarbodiimideHCID 56840192N-[(2,4-dichloro-3-isothiocyanatophenyl)methyl]-2,2-dimethylpropanamideHCID 178507781HCID 178507781, compound

Product 1

HCID 178447325HCID 178447325, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of N-(trans-4-trifluoromethyl-cyclohex-1-yl)-2-(difluoromethoxy)-5-amino-4-nitro-benzoic acid amide (70 mg, 0.176 mmol), Pd/C (15 mg) and 10 mL THF is stirred under a H2-atmosphere (3 bar) for 2 h. The crude mixture is filtered into a flask charged with N-(2,4-dichloro-3-isothiocyanato-benzyl)-2,2-dimethyl-propionamide (59 mg, 0.185 mmol) and the filter cake is washed with 40 mL THF. The mixture is stirred for 4 h at rt and overnight at 60° C. Then the reaction mixture is concentrated to −10 mL and stirred for additional 8 h at 60° C. Then it is concentrated i. vac., diluted with MeCN (2.0 mL) and DIC (29 μl, 0.186 mmol) is added and it is stirred for 4 d. Then the mixture is concentrated, diluted with DMF and THF and purified via HPLC.

Workup

  1. filtrationThe crude mixture is filtered into a flask
  2. washthe filter cake is washed with 40 mL THF
  3. stirringThe mixture is stirred for 4 h at rt and overnight at 60° C
  4. concentrationThen the reaction mixture is concentrated to −10 mL
  5. stirringstirred for additional 8 h at 60° C
  6. concentrationThen it is concentrated i
  7. additionis added
  8. stirringit is stirred for 4 d
  9. concentrationThen the mixture is concentrated
  10. additiondiluted with DMF and THF
  11. custompurified via HPLC

Sources & evidence

ORD record
ord-5f8bf267b47b46b38a2f982296840cc6
Source dataset
uspto-grants-2014_06
Patent number
US08759537B2

Reaction notes

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