1-Butanol → HCID 58094763, compound

HRID 2282147Notes

Reaction equation

HRID 2282147 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:26]#[N:27])=[C:11]([C:19]2[CH:24]=[CH:23][N:22]=[C:21](F)[CH:20]=2)[S:12][C:13]=1[C:14]1[NH:18][N:17]=[CH:16][CH:15]=1.COC1C=C(OC)C=CC=1C[NH2:33].CCN(C(C)C)C(C)C.C(O)CCC.C(Cl)Cl.C(O)(C(F)(F)F)=O>>[NH2:33][C:21]1[CH:20]=[C:19]([C:11]2[S:12][C:13]([C:14]3[NH:18][N:17]=[CH:16][CH:15]=3)=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[C:10]=2[C:26]#[N:27])[CH:24]=[CH:23][N:22]=1

Participants

7

Reactant 6

HCID 2631-ButanolHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 5972502,4-DimethoxybenzylamineHCID 58094733HCID 58094733, compound

Product 1

HCID 58094763HCID 58094763, compoundYield 100.7%

Procedure

4-(2,4-dichlorophenyl)-2-(2-fluoropyridin-4-yl)-5-(1H-pyrazol-5-yl)thiophene-3-carbonitrile (0.372 g, 0.903 mmol), 2,4-dimethoxybenzylamine (821 mg, 4.91 mmol) and DIPEA (317 mg, 2.46 mmol) in 1-Butanol (3.74 mL, 40.9 mmol) was irradiated in microwave at 160° C. for 2 hr under nitrogen. The solvent was evaporated and the residue was purified by column chromatography to afford an intermediate which was in the next step. LC/MS (FA) ES+ 562, 564. The above intermediate was dissolved in DCM (26 mL, 4.0E2 mmol) and TFA (8.5 mL, 110 mmol). The mixture was stirred at rt for 30 min. The mixture was concentrated and the residue was basified by ammonium hydroxide. The solvent was evaporated and the mixture was purified by column chromatography to afford the title compound (0.375 g, 100%). LC/MS (FA) ES+ 412, 414. 1H NMR (400 MHz, d4-methanol) δ: 8.00 (1H, d, J=6.62 Hz), 7.77 (1H, d, J=2.01 Hz), 7.59 (1H, d, J=2.45 Hz), 7.56 (1H, dd, J=8.26, 2.02 Hz), 7.49 (1H, d, J=8.27 Hz), 7.38 (1H, d, J=1.59 Hz), 7.24 (1H, dd, J=6.64, 1.77 Hz), 5.58 (1H, d, J=2.38 Hz)

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by column chromatography
  3. customto afford an intermediate which
  4. concentrationThe mixture was concentrated
  5. customThe solvent was evaporated
  6. customthe mixture was purified by column chromatography

Sources & evidence

ORD record
ord-d13df3222f7b452a89461c0c7830acdb
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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