1,2-Dichloroethane → HCID 25191867, compound

HRID 388486Notes

Reaction equation

HRID 388486 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([C@H:24]([CH2:28][CH2:29][CH3:30])[C:25](O)=[O:26])[C:14]2=[O:31])=[CH:3]1.N.C1C=CC2N(O)N=[N:39]C=2C=1.C(Cl)CCl>C1COCC1.O1CCOCC1.O.CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([C@H:24]([CH2:28][CH2:29][CH3:30])[C:25]([NH2:39])=[O:26])[C:14]2=[O:31])=[CH:3]1

Participants

9

Reactant 4

HCID 111,2-Dichloroethane2×HCID 222Ammonia2×HCID 757711-HydroxybenzotriazoleHCID 68749245HCID 68749245, compound

Product 1

HCID 25191867HCID 25191867, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To the suspension of (R)-2-[1-(1,4-Dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-pentanoic acid (95 mg, 0.23 mmol), (prepared according to example 4) in THF (2.5 mL) at room temperature are added 0.5 M NH3 in 1,4-dioxane solution (0.91 mL, 0.45 mmol) and HOBt (15 mg, 0.11 mmol). Then EDC (87 mg, 0.45 mmol) is added in small portions. The reaction mixture is stirred for 16 hours and then DMF (1.0 mL) along with another 0.5 M NH3 (1.0 mL) in 1,4-dioxane solution and EDC (87 mg, 0.45 mmol) are added. The reaction is continued for another 60 hours. Then water (55 mL) is added and the mixture is extracted with EtOAc (3×30 mL). The organic layers are combined, dried over Na2SO4 and are concentrated to give crude product. Purification by flash column chromatography using 6% MeOH in DCM followed by washing using Methanol affords the title compound. LCMS (ESMS): m/z 419.77 (M+H+).

Workup

  1. waitThe reaction is continued for another 60 hours
  2. extractionthe mixture is extracted with EtOAc (3×30 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationare concentrated
  5. customto give crude product
  6. customPurification by flash column chromatography
  7. washby washing

Sources & evidence

ORD record
ord-617ac939102944aeb116ce619d7173f0
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

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