4-Methylmorpholine → (3S)-2-[(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-methyl-N-[3-(methyloxy)-2-pyrazinyl]-3-pyrazolidinecarboxamide

HRID 1396890노트

반응식

HRID 1396890 반응식
CN1CCOCC1.[CH:8]1([CH2:13][C@H:14]([CH2:35][N:36]([CH:45]=[O:46])[O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:15]([N:17]2[C@H:21]([C:22](O)=[O:23])[CH2:20][CH2:19][N:18]2[C:25](OCC2C=CC=CC=2)=O)=[O:16])[CH2:12][CH2:11][CH2:10][CH2:9]1.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[CH3:64][O:65][C:66]1[C:67]([NH2:72])=[N:68][CH:69]=[CH:70][N:71]=1>C(#N)C.CN(C=O)C>[CH:8]1([CH2:13][C@H:14]([CH2:35][N:36]([CH:45]=[O:46])[O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:15]([N:17]2[C@H:21]([C:22]([NH:72][C:67]3[C:66]([O:65][CH3:64])=[N:71][CH:70]=[CH:69][N:68]=3)=[O:23])[CH2:20][CH2:19][N:18]2[CH3:25])=[O:16])[CH2:9][CH2:10][CH2:11][CH2:12]1

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 27340604-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-iumHCID 124898513-Methoxypyrazin-2-amineHCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

생성물 1

HCID 86706354(3S)-2-[(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-methyl-N-[3-(methyloxy)-2-pyrazinyl]-3-pyrazolidinecarboxamide수율 51%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

반응 조건

온도
0 °C

실험 절차

4-Methylmorpholine (47.4 μl, 0.431 mmol) was added into a solution of (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (150 mg, 0.359 mmol) and 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (141 mg, 0.431 mmol) in acetonitrile (5.94 ml). The resulting solution was cooled to 0° C. and stirred at 0° C. for 15 min. To the reaction mixture was added 3-(methyloxy)-2-pyrazinamine (67.4 mg, 0.539 mmol). The reaction mixture was stirred for 2 days at rt. The reaction mixture was concentrated in vacuo and the residue was dissolved in DCM, washed with saturated NaHCO3 solution, followed by brine. The solution was dried over sodium sulfate and filtered. The solvent was removed to give a residue which was redissolved in DMF (3.75 ml) and purified by RP-HPLC to afford (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-methyl-N-[3-(methyloxy)-2-pyrazinyl]-3-pyrazolidine carboxamide (96 mg, 0.183 mmol, 51% yield) as a white solid. LC-MS (ES) m/e 525.5 (M+H)+.

후처리

  1. stirringThe reaction mixture was stirred for 2 days at rt
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in DCM
  4. washwashed with saturated NaHCO3 solution
  5. dry with materialThe solution was dried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed
  8. customto give a residue which
  9. custompurified by RP-HPLC

출처 및 근거

ORD 기록
ord-a1fd517b59234f6db7c2f0edf4be1f7c
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901119B2

반응 노트

불러오는 중…