Dimethylformamide → HCID 67705207, compound

HRID 363207Notes

Reaction equation

HRID 363207 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14]C(CC1C=CC=CC=1)C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1[C:32](=O)[C:31]2[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=2N=N1.Cl.CN(C)CCCN=C=N[CH2:47][CH3:48].Cl.[CH3:51][O:52][C:53](=[O:60])[C@H:54]([CH2:56][CH2:57][S:58][CH3:59])[NH2:55].CCN(CC)CC.CN(C=[O:72])C>CCOC(C)=O>[CH3:51][O:52][C:53](=[O:60])[C@@:54]([O:14][CH2:13][C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])([CH2:56][CH2:57][S:58][CH3:59])[NH:55][C:47](=[O:72])[CH2:48][CH2:32][C:31]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:30]=1

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 86751188HCID 86751188, compound

Product 1

HCID 67705207HCID 67705207, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2(R and S)-[1-(t-butoxycarbonyl)-pyrrolidin-2(S)-ylmethyloxy]-3-phenylpropionic acid (263.6 mg, 0.754 mmol) in DMF (8.0 mL) were added 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (HOOBT, 137 mg, 0.840 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 164 mg, 0.855 mmol), L-methionine methyl ester hydrochloride (176 mg, 0.881 mmol), and Et3N (0.35 mL, 2.5 mmol). The reaction was stirred under argon at ambient temperature for 18 h, diluted with EtOAc (70 mL), and washed with 10% aq citric acid (70 mL), saturated aq NaHCO3 (40, 20 mL), and saturated aq NaCl (40 mL). The organic layer was dried (Na2SO4) and evaporated in vacuo. The diastereomeric crude products were purified and separated by chromatography (silica gel, 1:19 to 1:2 EtOAc/CH2Cl2) to give the title compound. 1H NMR (CD3OD, 400 MHz) δ7.35-7.17 (m, 5H), 4.63-4.55 (m, 1H), 4.08-3.90 (m, 2H), 3.72 (s, 3H), 3.55-3.46 (m, 2H), 3.34-3.22 (m, 1H), 3.09 (dd, J=14, 4 Hz, 1H), 2.91 (dd, J=14, 7 Hz, 1H), 2.38-2.20 (m, 2H), 2.10-2.00 (m, 1H), 2.04 (br s, 3H), 1.97-1.86 (m, 6H), 1.44 (s, 9H).

Workup

  1. washwashed with 10% aq citric acid (70 mL), saturated aq NaHCO3 (40, 20 mL), and saturated aq NaCl (40 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. customevaporated in vacuo
  4. customThe diastereomeric crude products were purified
  5. customseparated by chromatography (silica gel, 1:19 to 1:2 EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-0316b099d24449feafd56746afc5d309
Source dataset
uspto-grants-1999_02
Patent number
US05872135

Reaction notes

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