Pyridine → HCID 53629560, compound

HRID 1990258Notes

Reaction equation

HRID 1990258 reaction equation
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[N:16]=[CH:17][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:30]=3)[C:25]([OH:27])=O)=[N:19][CH:20]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[N:16]=[CH:17][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:30]=3)[C:25]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=3)=[O:27])=[N:19][CH:20]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 104392-AminopyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 591271113-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid

Product 1

HCID 53629560HCID 53629560, compoundYield 18.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.080 mL, 0.6 mmol) was added to a solution of 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid (193 mg, 0.50 mmol) in DCM (10 mL) and stirred at RT for 30 minutes. 2-Aminopyridine (57 mg, 0.6 mmol) and pyridine (0.082 mL, 1 mmol) were added and the reaction stirred for a further 16 hours. The solvent was removed in vacuo and the residue was taken up in ethyl acetate (50 mL). The organic phase was washed with water (2×20 mL), 1N citric acid (10 mL), water (10 mL), a saturated aqueous solution of sodium bicarbonate (10 mL) and brine (100 mL), then dried (MgSO4), filtered, and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 50-80% ethyl acetate in isohexane, to give the desired compound as a white foam (42 mg). 1H NMR δ (CDCl3): 1.28 (d, 3H), 2.31 (quin, 2H), 3.34 (s, 3H), 3.43-3.56 (m, 2H), 4.19 (t, 2H), 4.57 (q, 1H), 4.62 (t, 2H), 6.90 (s, 1H), 7.03 (t, 1H), 7.20 (s, 1H), 7.36 (s, 1H), 7.71 (t, 1H), 8.23 (d, 1H), 8.28 (s, 1H), 8.30 (d, 1H), 8.64 (s, 1H), 8.79 (s, 1H); m/z 464 (M+H)+

Workup

  1. stirringthe reaction stirred for a further 16 hours
  2. customThe solvent was removed in vacuo
  3. washThe organic phase was washed with water (2×20 mL), 1N citric acid (10 mL), water (10 mL)
  4. dry with materiala saturated aqueous solution of sodium bicarbonate (10 mL) and brine (100 mL), then dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was chromatographed on silica
  8. washeluting with a gradient of 50-80% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-cb1f1b8775064e8e987ceb1e6fe7bd6e
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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