Ammonia → HCID 59349652, compound

HRID 2170985Notes

Reaction equation

HRID 2170985 reaction equation
[CH2:1]([O:3][C:4]1[N:13]=[CH:12][C:11]([CH3:14])=[C:10]2[C:5]=1[CH:6]([C:19]1[CH:20]=[CH:21][CH:22]=[C:23]3[C:28]=1[O:27][C:26]([CH3:29])=[CH:25][C:24]3=[O:30])[C:7]([C:16](O)=[O:17])=[C:8]([CH3:15])[NH:9]2)[CH3:2].C(OCC)(=O)C.C(N1C=CN=C1)([N:39]1C=CN=C1)=O.N>CN(C=O)C>[CH2:1]([O:3][C:4]1[N:13]=[CH:12][C:11]([CH3:14])=[C:10]2[C:5]=1[CH:6]([C:19]1[CH:20]=[CH:21][CH:22]=[C:23]3[C:28]=1[O:27][C:26]([CH3:29])=[CH:25][C:24]3=[O:30])[C:7]([C:16]([NH2:39])=[O:17])=[C:8]([CH3:15])[NH:9]2)[CH3:2]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 59349653HCID 59349653, compound

Product 1

HCID 59349652HCID 59349652, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

335.0 mg (0.824 mmol) of the compound from Example 41A are introduced into 10 ml of ethyl acetate, and 167.1 mg (0.537 mmol) of 1,1′-carbonyldiimidazole are added. The suspension is then stirred at room temperature overnight. Since a clear solution is not produced, 2 ml of DMF are added and the mixture is stirred at room temperature for a further two hours. Complete conversion is then established by TLC check. The volatile components are removed in a rotary evaporator, and the residue is taken up in 4 ml of DMF. Then 2.293 ml of ammonia (28% by weight solution in water, 16.5 mmol) and 10.1 mg of 4-N,N-dimethylaminopyridine are added. The reaction mixture is heated at 100° C. in a closed vessel for thirty minutes. After cooling, the solvent is removed under reduced pressure, and the residue is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). The product fractions are concentrated and the residue is taken up in a little dichloromethane, and diisopropyl ether is added until the solution is cloudy. The precipitated solid is isolated and dried in vacuo. 207 mg (59% of theory) of the title compound are obtained.

Workup

  1. additionare added
  2. customSince a clear solution is not produced
  3. stirringthe mixture is stirred at room temperature for a further two hours
  4. customThe volatile components are removed in a rotary evaporator
  5. temperatureThe reaction mixture is heated at 100° C. in a closed vessel for thirty minutes
  6. temperatureAfter cooling
  7. customthe solvent is removed under reduced pressure
  8. customthe residue is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)
  9. concentrationThe product fractions are concentrated
  10. additionis added until the solution
  11. customThe precipitated solid is isolated
  12. customdried in vacuo

Sources & evidence

ORD record
ord-924ccdc9e2a8407cafc1bed0feabe5ef
Source dataset
uspto-grants-2015_06
Patent number
US09051316B2

Reaction notes

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