Pyridine → 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-N-pyrazin-2-yl-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 1011818Notes

Reaction equation

HRID 1011818 reaction equation
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[N:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][O:34][CH2:33]4)[CH:30]=3)[C:25]([OH:27])=O)=[CH:17][CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:37][C:38]1[CH:43]=[N:42][CH:41]=[CH:40][N:39]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[N:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][O:34][CH2:33]4)[CH:30]=3)[C:25]([NH:37][C:38]3[CH:43]=[N:42][CH:41]=[CH:40][N:39]=3)=[O:27])=[CH:17][CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 78747AminopyrazineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 536296783-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid

Product 1

HCID 536295763-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-N-pyrazin-2-yl-5-[(3S)-tetrahydrofuran-3-yloxy]benzamideYield 23.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.095 mL, 0.75 mmol) was added to a solution of 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (250 mg, 0.65 mmol) in DCM (6 mL) and stirred at RT for 30-40 minutes. 2-Aminopyrazine (125 mg, 1.31 mmol) and pyridine (0.106 mL, 1.31 mmol) were added and the reaction stirred at RT for 2 hours. The solvent was removed in vacuo, water (20 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The organic extracts were combined and washed with 2N hydrochloric acid (20 mL), a saturated solution of sodium bicarbonate (20 mL), water (20 mL), brine (20 mL), dried (MgSO4) and evaporated in vacuo. The crude product was chromatographed on silica, eluting with a gradient of 0-10% methanol in DCM, to give the desired compound (71 mg).

Workup

  1. stirringthe reaction stirred at RT for 2 hours
  2. customThe solvent was removed in vacuo, water (20 mL)
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  5. washwashed with 2N hydrochloric acid (20 mL)
  6. dry with materiala saturated solution of sodium bicarbonate (20 mL), water (20 mL), brine (20 mL), dried (MgSO4)
  7. customevaporated in vacuo
  8. customThe crude product was chromatographed on silica
  9. washeluting with a gradient of 0-10% methanol in DCM

Sources & evidence

ORD record
ord-7e97abae18f6497181800488fa760988
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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