Morpholine → 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid

HRID 613863노트

반응식

HRID 613863 반응식
C([O:4][C:5](=[O:36])[CH2:6][C@@H:7]([N:20]1[CH:24]=[CH:23][C:22]([C:25](=[O:35])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)=[CH:21]1)[C:8]([NH:10][C@H:11]([C:16](=[O:19])[NH:17][CH3:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:9])C=C.N1CCOCC1>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][C:25]([C:22]2[CH:23]=[CH:24][N:20]([C@@H:7]([C:8]([NH:10][C@H:11]([C:16](=[O:19])[NH:17][CH3:18])[C:12]([CH3:15])([CH3:13])[CH3:14])=[O:9])[CH2:6][C:5]([OH:36])=[O:4])[CH:21]=2)=[O:35])=[CH:28][CH:29]=1)#[N:34]

참가 물질

5

반응물 2

HCID 8083MorpholineHCID 700987653(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester

생성물 1

HCID 539761643(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid수율 107.2%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6342Acetonitrile용매

실험 절차

Routine allyl ester cleavage conditions were previously described by Friedrich-Bochnitschek, S.; Waldmann, H.; Kunz, H. J. Org. Chem. 1989, 54, 751-756. To a solution of 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester (247 mg, 0.501 mmol) in acetonitrile (2 mL) was added in succession Pd(PPh3)4 (29 mg, 0.026 mmol) and morpholine (226 μL, 2.60 mmol). The resultant mixture was carefully purged with argon. After 30 min, the resultant green mixture was stirred with 10% aqueous KHSO4 (20 mL) and extracted with CHCl3 (35 mL). The organic layer was washed with 10% aqueous KHSO4 (20 mL), dried over Na2SO4, and concentrated. Flash column chromatography with 1% HOAc/3% MeOH/CHCl3 and drying via azeotrope with n-heptane gave 243 mg (94%) of 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid as a yellow solid. 1H NMR (CD3OD): δ 8.09 (d, 1H, J=8.7 Hz), 8.05 (dd, 1H, J=2.8, 6.9 Hz), 7.78 (dd, 1H, J=1.9, 1.9 Hz), 7.66 (d, 2H, J=8.4 Hz), 7.46 (d, 2H, J=8.4 Hz), 6.90 (dd, 1H, J=2.2, 2.2 Hz), 6.59 (dd, J=1.9, 3.1 Hz), 5.33 (t, 1H, J=7.5 Hz), 4.22-4.15 (m, 3H), 3.24 (t, 1H, J=8.7 Hz), 2.98 (dd, 1H, J=5.3, 17.4 Hz), 2.66 (d, 3H, J=4.7 Hz), 0.99 (s, 9H). IR (KBr): 3332, 2696, 2230, 1719, 1654, 1532, 1412, 1177 cm-1. HRFABMS: Calculated for C24H29N4O5 (M+H+): 453.2125. Found: 453.2125. Anal. Calculated for C24H28N4O5.0.5 HOAc.0.3 CHCl3 : C, 58.62; H, 5.89; N, 10.81. Found: C, 58.41; H, 5.72; N, 10.50.

후처리

  1. customThe resultant mixture was carefully purged with argon
  2. extractionextracted with CHCl3 (35 mL)
  3. washThe organic layer was washed with 10% aqueous KHSO4 (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dry with materialFlash column chromatography with 1% HOAc/3% MeOH/CHCl3 and drying via azeotrope with n-heptane

출처 및 근거

ORD 기록
ord-41271cd679e242aea6c7d6de1cdbffff
출처 데이터셋
uspto-grants-1999_12
특허 번호
US06008243

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