1-Butanol → HCID 178509409, compound

HRID 2282138Notes

Reaction equation

HRID 2282138 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]=[N: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]=[N: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 178509407HCID 178509407, compound

Product 1

HCID 178509409HCID 178509409, compoundYield 47%

Procedure

A solution of 4-(2,4-dichlorophenyl)-2-(2-fluoropyridin-4-yl)-5-(1H-1,2,3-triazol-5-yl)thiophene-3-carbonitrile (0.103 g, 0.247 mmol), 2,4-dimethoxybenzylamine (0.247 g, 1.48 mmol) and DIPEA (0.0959 g, 0.742 mmol) in 1-Butanol (15 g, 2.0E2 mmol) was irradiated in microwave at 170° C. for 2 hrs. The mixture was concentrated and the residue was purified by column chromatography to afford desired intermediate. LC/MS (FA) ES+ 563, 565. To the intermediate in DCM (5.9 mL, 93 mmol) was added TFA (2 mL, 20 mmol) and the mixture was stirred for 10 min. The reaction mixture was concentrated and the residue in MeOH was treated with sodium bicarbonate and water. The mixture was concentrated and the mixture was purified by column chromatography to afford the title compound (48 mg, 47.0%). LC/MS (FA) ES+ 413, 415. 1H NMR (400 MHz, d4-methanol) δ: 8.03 (1H, d, J=6.26 Hz), 7.74 (1H, d, J=1.93 Hz), 7.54 (1H, dd, J=8.27, 1.97 Hz), 7.46 (1H, d, J=8.26 Hz), 7.05 (1H, s), 7.01 (2H, m)

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by column chromatography
  3. customto afford desired intermediate
  4. concentrationThe reaction mixture was concentrated
  5. additionthe residue in MeOH was treated with sodium bicarbonate and water
  6. concentrationThe mixture was concentrated
  7. customthe mixture was purified by column chromatography

Sources & evidence

ORD record
ord-2f51ca4d7f7c4b5082873c49046290a4
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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