Water → HCID 178523379, compound

HRID 1640596Notes

Reaction equation

HRID 1640596 reaction equation
[CH2:1]([O:8][C:9](=[O:29])[NH:10][CH2:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18](=O)[NH:19][CH2:20][C:21]2[C:26]([Cl:27])=[N:25][CH:24]=[CH:23][N:22]=2)[CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+].O>CCOC(C)=O.CN(C=O)C>[CH2:1]([O:8][C:9](=[O:29])[NH:10][CH2:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]2[N:22]3[CH:23]=[CH:24][N:25]=[C:26]([Cl:27])[C:21]3=[CH:20][N:19]=2)[CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178523386HCID 178523386, compound

Product 1

HCID 178523379HCID 178523379, compoundYield 109.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of benzyl[(trans-4-{[(3-chloropyrazin-2-yl)methyl]carbamoyl}cyclohexyl)methyl]carbamate (0.100 g, 0.220 mmol) in EtOAc (0.9 mL) and DMF (0.068 mL) at 0° C. was added slowly POCl3 (0.082 mL, 0.88 mmol). After stirring at rt for an hour, the mixture was cooled to 0° C. and solid NaHCO3 was added. After a further 10 min at 0° C. and 20 min at rt, the mixture was re-cooled to 0° C. and water (20 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the extracts washed with water (2×30 mL) and brine (30 mL) and then dried over Na2SO4 and concentrated in vacuo to afford 0.096 g of the title compound. 1H NMR (400 MHz, CDCl3): δ 1.15-1.19 (m, 2H), 1.76-1.87 (m, 3H), 1.93-2.00 (m, 2H), 2.04-2.08 (m, 2H), 3.07 (m, 1H), 3.15 (t, J=6.4 Hz, 2H), 4.84 (br, 1H), 5.09 (s, 2H), 7.31-7.40 (m, 6H), 7.61 (d, J=4.8 Hz, 1H), 7.79 (s, 1H). MS (ES+): m/z 399.26 [MH+].

Workup

  1. temperaturethe mixture was cooled to 0° C.
  2. temperature20 min at rt, the mixture was re-cooled to 0° C.
  3. extractionThe reaction mixture was extracted with EtOAc (3×20 mL)
  4. washthe extracts washed with water (2×30 mL) and brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8fe45d70707446f0978e5f595ab8396d
Source dataset
uspto-grants-2012_02
Patent number
US08114846B2

Reaction notes

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