Ethyl Acetate → HCID 67497382, compound

HRID 1628344Notes

Reaction equation

HRID 1628344 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:25][CH2:26][C:27](O)=[O:28])[C:10]([NH:12][C:13]2[N:17]([CH3:18])[N:16]=[C:15]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[CH:14]=2)=[O:11])=[CH:4][CH:3]=1.C(OCC)(=O)C.Cl.[CH2:37]([NH2:39])[CH3:38].[Cl-].[NH4+]>C(N(CC)CC)C.ClCCl>[CH2:37]([NH:39][C:27]([CH2:26][NH:25][C@@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:10]([NH:12][C:13]1[N:17]([CH3:18])[N:16]=[C:15]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[CH:14]=1)=[O:11])=[O:28])[CH3:38]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11198Ethylamine hydrochlorideHCID 25517Ammonium ChlorideHCID 46869362HCID 46869362, compound

Product 1

HCID 67497382HCID 67497382, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a 25 ml flask was added 2-((S)-3-(4-fluorophenyl)-1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid 103.2 (145 mg, 0.36 mmole), 50% propylphosphoric anhydride in ethyl acetate (348 mg, 0.55 mmole), 0.2 ml of triethylamine and 3 ml of dichloromethane. After 20 min, ethylamine hydrochloride (60 mg, 0.73 mmole) was added to the mixture. The reaction was stirred at room temperature for 4 days. The solution was poured into saturated ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. After concentration in vacuo, the residue was chromatographed on silica gel to give 103.3 (69 mg, 44% yield) as colorless amorphous. LCMS ESI (pos.) m/e: 425 (M+H); 1H NMR (400 MHz, DMSO-d6) δ ppm 9.91 (s, 1H), 8.58 (dd, J=17.9, 6.2 Hz, 2H), 7.63 (dd, J=19.5, 6.2 Hz, 2H), 7.25 (dd, J=9.2, 6.0 Hz, 2H), 7.05 (t, J=7.7 Hz, 2H), 6.82 (s, 1H), 5.79 (brs, 1H), 3.81 (s, 3H), 3.46 (dd, J=8.6, 4.7 Hz, 1H), 3.31-3.17 (m, 3H), 3.21 (d, J=2.8 Hz, 2H), 2.92 (dd, J=14.1, 8.6 Hz, 1H), 1.09 (t, J=7.2 Hz, 3H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationAfter concentration in vacuo
  5. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-84eaf9493f10427889d265ba2bb95715
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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