Pyridine → HCID 18009485, compound

HRID 987604Notes

Reaction equation

HRID 987604 reaction equation
CO[C:3]([CH:5]1[CH2:10][CH2:9][C:8]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([CH2:11][NH:12][C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][C:22]#C)=[O:14])[CH2:7][CH2:6]1)=[O:4].O=S(Cl)Cl.[C:34]([O-:37])(O)=O.[Na+].N1C=CC=C[CH:40]=1>>[C:34]([O:4][CH2:3][C:5]1[CH2:10][CH2:9][C:8]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([CH2:11][NH:12][C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][CH3:22])=[O:14])[CH2:7][CH:6]=1)(=[O:37])[CH3:40]

Participants

5

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 68831233HCID 68831233, compound

Product 1

HCID 18009485HCID 18009485, compound

Procedure

To a solution of 1-hydroxy-1-acetoxymethyl)-4-phenyl-4-(3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl)-cyclohexane (Example 171, isomer #1, 19.5 mg, 0.047 mmol) in 2 mL of pyridine was added SOCl2 (0.2 mL, 2.7 mmol) at 0° C. and the mixture was stirred at rt for 1 h. It was then poured into NaHCO3, extracted with CH2Cl2 (2×), dried over MgSO4 filtered and concentrated. The residue was purified by HPLC (Waters RCM, μ Porosil, 25 mm×10 cm) using a mixture of (5:4:1 hexane-methyl tert-butyl ether-acetonitrile:hexane, 7.75/6.0 mL/min) to give the title compound. 1H NMR (CDCl3) δ 8.18 (d, 1H, J=7.8 Hz), 7.60 (bs, 1H), 7.26-7.41 (m, 6H), 7.03 (t, 1H, J=7.6 Hz), 6.83 (d, 1H, J=8.3 Hz), 5.81 (s, 1H), 4.39-4.45 (m, 2H), 3.80 (d of d, 1H, J=6.4, 13.2 Hz), 3.75 (d of d, 1H, J=6.4, 13.2 Hz), 3.15 (s, 3H), 2.61 (d, 1H, J=17.7 Hz), 2.38 (d, 1H, J=17.7), 2.04 (s, 3H), 1.77-2.16 (m, 4H); Mass Spectrum (CI) m/e 394 (M+1).

Workup

  1. extractionextracted with CH2Cl2 (2×)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by HPLC (Waters RCM, μ Porosil, 25 mm×10 cm)
  6. additiona mixture of (5:4:1 hexane-methyl tert-butyl ether-acetonitrile:hexane, 7.75/6.0 mL/min)

Sources & evidence

ORD record
ord-9054c6a7ef194ec5920a5ee17e8c6dc0
Source dataset
uspto-grants-2003_10
Patent number
US06632836B1

Reaction notes

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