2-(1H-1,2,3-Triazol-1-yl)ethanamine → N-(2-(1H-1,2,3-Triazol-1-yl)ethyl)-5-fluoro-4-(7-(2-fluoro-5-methylpyridin-4-yl)benzo[b]thiophen-2-yl)pyrimidin-2-amine

HRID 1640925Notes

Reaction equation

HRID 1640925 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]3[C:13]([C:17]4[C:22]([CH3:23])=[CH:21][N:20]=[C:19]([F:24])[CH:18]=4)=[CH:14][CH:15]=[CH:16][C:10]=3[CH:9]=2)[C:5]([F:25])=[CH:4][N:3]=1.[N:26]1([CH2:31][CH2:32][NH2:33])[CH:30]=[CH:29][N:28]=[N:27]1>C(O)CCC.O1CCOCC1.O1CCOCC1.CN1C(=O)CCC1.CN1C(=O)CCC1.C(Cl)(Cl)Cl.C(O)(C)C>[N:26]1([CH2:31][CH2:32][NH:33][C:2]2[N:7]=[C:6]([C:8]3[S:12][C:11]4[C:13]([C:17]5[C:22]([CH3:23])=[CH:21][N:20]=[C:19]([F:24])[CH:18]=5)=[CH:14][CH:15]=[CH:16][C:10]=4[CH:9]=3)[C:5]([F:25])=[CH:4][N:3]=2)[CH:30]=[CH:29][N:28]=[N:27]1

Participants

8

Reactant 2

HCID 225619722-(1H-1,2,3-Triazol-1-yl)ethanamineHCID 866418792-Chloro-5-fluoro-4-[7-(2-fluoro-5-methyl-pyridin-4-yl)-benzo[b]thiophen-2-yl]-pyrimidine

Product 1

HCID 25120564N-(2-(1H-1,2,3-Triazol-1-yl)ethyl)-5-fluoro-4-(7-(2-fluoro-5-methylpyridin-4-yl)benzo[b]thiophen-2-yl)pyrimidin-2-amineYield 59%

Reagents, catalysts & solvents 5

HCID 2631-ButanolSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 312751,4-DioxaneSolventHCID 17800835dioxane NMPSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
135 °C

Procedure

Combine 2-chloro-5-fluoro-4-[7-(2-fluoro-5-methyl-pyridin-4-yl)-benzo[b]thiophen-2-yl]-pyrimidine (200 mg, 0.54 mmol) and 2-[1,2,3]triazol-1-yl-ethylamine (120 mg, 21.1 mmol) in n-butanol (2 mL), alternative dioxane, dioxane-NMP (N-methylpyrrolidinone), NMP alone as solvent] in a pressure vessel. Heat the mixture in an oil bath at 120-150° C. overnight (or in microwave reactor for 10-60 min). Dilute the mixture with chloroform/IPA (3/1). Wash the solution with saturated aqueous sodium chloride, dry over sodium sulfate, and concentrate the solution in vacuo to a dark residue. Purify by column chromatography (DCM→10% methanol in DCM) to afford the title compound as a yellow solid (140 mg, 59%). MS (ES) m/z 450 [M+1]+.

Workup

  1. washWash the solution with saturated aqueous sodium chloride
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate the solution in vacuo to a dark residue
  4. customPurify by column chromatography (DCM→10% methanol in DCM)

Sources & evidence

ORD record
ord-d4f79ab69d85409a8e1321dcbb984611
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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