Water → HCID 22479128, compound

HRID 1392188Notes

Reaction equation

HRID 1392188 reaction equation
[Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][C:7]23[C:15](=[O:16])[N:14]([C:17]4[CH:22]=[C:21]([Cl:23])[N:20]=[C:19]([Cl:24])[CH:18]=4)[C:13](=[O:25])[N:12]2[NH:11][CH2:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:37][O:38][C:39](Cl)=[O:40].O>C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][C:7]23[C:15](=[O:16])[N:14]([C:17]4[CH:22]=[C:21]([Cl:23])[N:20]=[C:19]([Cl:24])[CH:18]=4)[C:13](=[O:25])[N:12]2[N:11]([C:39]([O:38][CH3:37])=[O:40])[CH2:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformate2×HCID 81531DiisopropylethylamineHCID 22479146HCID 22479146, compound

Product 1

HCID 22479128HCID 22479128, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the compound from Example 100 (60 mg) in dry THF (2 mL) was added DIEA (0.044 mL), methylchloroformate (0.02 mL) and DMAP (catalytic amount). The reaction mixture was heated at 80° C. for 3 days during which more methylchloroformate (0.1 mL) was added after 24 hours and 48 hours. Water (10 mL) and EtOAc (10 mL) were added and the mixture shaken. The aqueous phase was separated and extracted with EtOAc. The combined organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography (silica gel; EtOAc/hexanes; chromatotron) to give the titled compound (37 mg). MS (m/z) 529 (MH+); Mp. 81° C.

Workup

  1. additionwas added after 24 hours and 48 hours
  2. customThe aqueous phase was separated
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography (silica gel; EtOAc/hexanes; chromatotron)

Sources & evidence

ORD record
ord-03fb6b686ec946b8b3c26d3a463825c9
Source dataset
uspto-grants-2008_03
Patent number
US07342012B2

Reaction notes

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