Hydrochloric Acid → 3-(5-tert-Butyloxazol-4-yl)-N-((S)-1-carbamoyl-2-phenylethyl)-2-hydroxyacrylamide

HRID 1917452Notes

Reaction equation

HRID 1917452 reaction equation
[C:1]([C:5]1[O:9][CH:8]=[N:7][C:6]=1[CH:10]=[C:11]([OH:15])[C:12]([OH:14])=O)([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:40][C@H:41]([C:49]([NH2:51])=[O:50])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(N(CC)CC)C>CN(C=O)C>[C:1]([C:5]1[O:9][CH:8]=[N:7][C:6]=1[CH:10]=[C:11]([OH:15])[C:12]([NH:40][C@H:41]([C:49](=[O:50])[NH2:51])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:14])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 445694Phenylalanine amideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665900433-(5-tert-Butyloxazol-4-yl)-2-hydroxyacrylic acid

Product 1

HCID 665902203-(5-tert-Butyloxazol-4-yl)-N-((S)-1-carbamoyl-2-phenylethyl)-2-hydroxyacrylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 3 (2.6 g, 12.3 mmol) in DMF was added HOBt.H2O (2.26 g, 14.76 mmol), EDC.HCl (2.80 g, 14.76 mmol), HCl.H-Phe-NH2 (3.16 g, 14.76 mmol), triethylamine (1.72 mL, 12.3 mmol) sequentially at 0° C. and the mixture was stirred for 14 h at room temperature. After the solvent was removed in vacuo, the residue was dissolved in AcOEt and washed with 5% citric acid, 5% NaHCO3 and saturated NaCl for three times, respectively. Then, the organic layer was dried over Na2SO4 and evaporated in vacuo. The resultant crude product was purified by silica-gel column chromatography (CHCl3:MeOH=100:1 to 10:1) to obtain the desired compound 4; yield 1.9 g (43.4%); m.p. 49-53° C.; 1H NMR (300 MHz, CDCl3) δ 11.04 (s, 1H), 7.82 (s, 1H), 7.34-7.22 (m, 5H), 6.24 (s, 1H), 5.96 (br s, 1H), 5.45 (br s, 1H), 4.78-4.71 (m, 1H), 3.24-3.11 (m, 2H), 1.38 (s, 9H); HRMS (EI): m/z 357.1689 (M+) (calced for C19H23N3O4: 357.1688).

Workup

  1. customAfter the solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in AcOEt
  3. washwashed with 5% citric acid, 5% NaHCO3 and saturated NaCl for three times
  4. dry with materialThen, the organic layer was dried over Na2SO4
  5. customevaporated in vacuo
  6. customThe resultant crude product was purified by silica-gel column chromatography (CHCl3:MeOH=100:1 to 10:1)

Sources & evidence

ORD record
ord-588993561c9443a3b84a56343369bc01
Source dataset
uspto-grants-2013_12
Patent number
US08618292B2

Reaction notes

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