Dimethylformamide → HCID 86711850, compound

HRID 623765Notes

Reaction equation

HRID 623765 reaction equation
CN([CH:4]=[O:5])C.O=P(Cl)(Cl)Cl.[CH2:11]([N:18]1[CH:22]=[C:21]([CH3:23])[C:20]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)=[C:19]1[C:31]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)=[O:32])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[CH2:11]([N:18]1[C:19]([C:31]([N:33]2[CH2:34][CH2:35][O:36][CH2:37][CH2:38]2)=[O:32])=[C:20]([C:24]2[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=2)[C:21]([CH3:23])=[C:22]1[CH:4]=[O:5])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 181649HOAtHCID 86711851HCID 86711851, compound

Product 1

HCID 86711850HCID 86711850, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of DMF (0.441 mL, 5.70 mmol) in DCM (5 mL) was added POCl3 (0.425 mL, 4.56 mmol). After stirring the reaction mixture at 0° C. for 15 min, a solution of (1-benzyl-3-(4-chlorophenyl)-4-methyl-1H-pyrrol-2-yl)(morpholino)methanone [obtained via standard EDI/HOAt coupling of ACI-02 with morpholine] (900 mg, 2.28 mmol) in DCM (1 mL) was dropwise added. The reaction was stirred for 30 min, then the ice-bath was removed and stirring was continued at room temperature for 1 h. The reaction mixture was cooled to 0° C., then saturated aqueous NaHCO3 was added while vigorously stirring, until the mixture was neutralised. The mixture was extracted with DCM, washed with brine and concentrated. The residue was dissolved in i-PrOH and precipitated with H2O. The precipitate was filtered, washed with i-PrOH/H2O (1:1, 2×) and MeOH (2×) and dried on for a couple of hours to give the desired product (761 mg, 79%).

Workup

  1. stirringThe reaction was stirred for 30 min
  2. customthe ice-bath was removed
  3. stirringstirring
  4. waitwas continued at room temperature for 1 h
  5. temperatureThe reaction mixture was cooled to 0° C.
  6. additionsaturated aqueous NaHCO3 was added
  7. stirringwhile vigorously stirring, until the mixture
  8. extractionThe mixture was extracted with DCM
  9. washwashed with brine
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in i-PrOH
  12. customprecipitated with H2O
  13. filtrationThe precipitate was filtered
  14. washwashed with i-PrOH/H2O (1:1, 2×) and MeOH (2×)
  15. customdried on for a couple of hours

Sources & evidence

ORD record
ord-5f671dd494b94518837fc865e443bdc1
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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