Acetic Acid → HCID 58095028, compound

HRID 2282144Notes

Reaction equation

HRID 2282144 reaction equation
[C:1]([C:3]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[Cl:15])=[C:6]([C:16]2[N:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH:18]=[CH:19][N:20]=2)[S:5][C:4]=1[C:29]1[CH:34]=[CH:33][N:32]=[C:31]([N:35](CC2C=CC(OC)=CC=2)[C:36](=[O:38])[CH3:37])[CH:30]=1)#[N:2].C(O)(=O)C.FC(F)(F)S(O)(=O)=O.C(Cl)Cl>C(#N)C.O.C(=O)=O.CO.C(Cl)Cl.C1(C)C=CC=CC=1>[C:1]([C:3]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[Cl:15])=[C:6]([C:16]2[N:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH:18]=[CH:19][N:20]=2)[S:5][C:4]=1[C:29]1[CH:34]=[CH:33][N:32]=[C:31]([NH:35][C:36](=[O:38])[CH3:37])[CH:30]=1)#[N:2]

Participants

10

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 62406Trifluoromethanesulfonic acid2×HCID 58095257HCID 58095257, compound

Product 1

HCID 58095028HCID 58095028, compoundYield 44.1%

Reagents, catalysts & solvents 5

HCID 280Carbon DioxideSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To the solution of [A] N-(4-{3-cyano-4-(2,4-dichlorophenyl)-5-[1-(4-fluorobenzyl)-1H-imidazol-2-yl]-2-thienyl}pyridin-2-yl)-N-(4-methoxybenzyl)acetamide (55.0 mg, 0.0806 mmol) in Acetic acid (1.0 mL, 18 mmol) was added Trifluoromethanesulfonic acid (0.10 mL, 1.1 mmol) and the mixture was stirred at r.t. for 20 hours. Methylene chloride (2.0 mL, 31 mmol) and Trifluoromethanesulfonic acid (0.10 mL, 1.1 mmol) were added and the mixture was stirred at r.t. for 20 hours. The mixture was rotovaped and azeotropped with toluene twice, dried in high vacuum. The residue was neutralized with aqueous saturated NaHCO3 to pH˜8, extracted with EtOAc. The EtOAc solution was dried over Na2SO4, filtered, evaporated in rotavapor to give a crude residue. Chromatograph in a silica column using MeOH/DCM (0/100 to 2/98) afforded a solid product. The product was dissolved in small amount of acetonitrile and ˜5 mL water, frozen in dry ice and lyophilized to give a powder product (20 mg, yield 44.1%). LCMS: (AA) ES+, 562, 564; FS−, 560, 562. 1H NMR (400 MHz, d1-methanol) δ: 8.62 (s, 1H), 8.47-8.48 (d, J=5.27 Hz, 1H), 7.53-7.55 (dd, J=5.27, 1.76 Hz, 1H), 7.47 (d, J=2.01 Hz, 1H), 7.33-7.36 (dd, J=8.28, 2.01 Hz, 1H), 7.26-7.27 (d, J=8.28 Hz, 1H), 7.16-7.19 (dd, J=7.28, 1.51 Hz, 2H), 6.98-7.02 (m, 2H), 6.83-6.86 (m, 2H), 4.98 (s, 2H), 2.21 (s, 3H).

Workup

  1. stirringthe mixture was stirred at r.t. for 20 hours
  2. customdried in high vacuum
  3. extractionextracted with EtOAc
  4. dry with materialThe EtOAc solution was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in rotavapor
  7. customto give a crude residue
  8. customafforded a solid product

Sources & evidence

ORD record
ord-aee0d42678b4431c81dc33002ff2b2d2
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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