1-Butanol → 2-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)phenoxy)ethanol

HRID 558153Notes

Reaction equation

HRID 558153 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]3[C:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH2:24][CH2:25][O:26]C4CCCCO4)=[CH:14][CH:15]=[CH:16][C:10]=3[CH:9]=2)[C:5]([F:33])=[CH:4][N:3]=1.[N:34]1([CH2:39][CH2:40][NH2:41])[CH:38]=[CH:37][N:36]=[N:35]1.O1CCOCC1.C(O)CCC>C(O)(C)(C)C.C(Cl)(Cl)Cl.C(O)(C)C.CN1C(=O)CCC1.O1CCOCC1.CN1C(=O)CCC1>[N:34]1([CH2:39][CH2:40][NH:41][C:2]2[N:7]=[C:6]([C:8]3[S:12][C:11]4[C:13]([C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=5[O:23][CH2:24][CH2:25][OH:26])=[CH:14][CH:15]=[CH:16][C:10]=4[CH:9]=3)[C:5]([F:33])=[CH:4][N:3]=2)[CH:38]=[CH:37][N:36]=[N:35]1

Participants

9

Reactant 4

HCID 2631-ButanolHCID 312751,4-DioxaneHCID 225619722-(1H-1,2,3-Triazol-1-yl)ethanamineHCID 866406622-Chloro-5-fluoro-4-(7-{2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-benzo[b]thiophen-2-yl)-pyrimidine

Product 1

HCID 592724752-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)phenoxy)ethanolYield 65%

Reagents, catalysts & solvents 4

HCID 6386tert-ButanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×HCID 17800835dioxane NMPSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
135 °C

Procedure

Combine 2-chloro-5-fluoro-4-(7-{2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-benzo[b]thiophen-2-yl)-pyrimidine (250 mg, 0.52 mmol) and 2-[1,2,3]triazol-1-yl-ethylamine (140 mg, 1.29 mmol) in tert-butanol (2.6 mL, alternative dioxane, n-butanol, dioxane-NMP, NMP alone as solvent) and NMP (1.3 mL) in a pressure vessel. Heat the mixture in an oil bath at 120-150° C. overnight (or in microwave reactor for a certain period of time). Dilute the mixture with chloroform/IPA (3/1). Wash the solution with aqueous saturated sodium chloride. Dry over sodium sulfate. Concentrate the solution in vacuo. Purify by column chromatography (DCM to 10% methanol in DCM) to give the title compound as a yellow solid (160 mg, 65%). MS (ES) m/z 477 [M+1]+.

Workup

  1. washWash the solution with aqueous saturated sodium chloride
  2. dry with materialDry over sodium sulfate
  3. concentrationConcentrate the solution in vacuo
  4. customPurify by column chromatography (DCM to 10% methanol in DCM)

Sources & evidence

ORD record
ord-7d6063710fb94076bf585c289e1ea82d
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

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