Triphenylphosphine → (1r)-Cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-3-methanesulfonyl-propyl]-3-oxo-2,3-dihydro-1h-isoindol-4-yl}-amide

HRID 1797236노트

반응식

HRID 1797236 반응식
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH2:34]([O:36][C:37]1[CH:38]=[C:39]([C@H:45]([N:49]2[C:57](=[O:58])[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][C:55]=3[NH:59][C:60]([CH:62]3[CH2:64][CH2:63]3)=[O:61])[CH2:50]2)[CH2:46][CH2:47]O)[CH:40]=[CH:41][C:42]=1[O:43][CH3:44])[CH3:35].[CH3:65][S-].[Na+].O[O:69][S:70]([O-:72])=O.[K+]>C1COCC1.CO.O>[CH2:34]([O:36][C:37]1[CH:38]=[C:39]([C@H:45]([N:49]2[C:57](=[O:58])[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][C:55]=3[NH:59][C:60]([CH:62]3[CH2:64][CH2:63]3)=[O:61])[CH2:50]2)[CH2:46][CH2:47][S:70]([CH3:65])(=[O:72])=[O:69])[CH:40]=[CH:41][C:42]=1[O:43][CH3:44])[CH3:35]

참가 물질

9

반응물 5

HCID 11776TriphenylphosphineHCID 4378561Sodium methanethiolateHCID 5363146Diisopropyl azodicarboxylateHCID 9845251(1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-3-hydroxy-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amideHCID 23707502Potassium hydroxy sulfite

생성물 1

HCID 10413135(1r)-Cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-3-methanesulfonyl-propyl]-3-oxo-2,3-dihydro-1h-isoindol-4-yl}-amide수율 5%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of triphenyl phosphine (0.63 g, 2.4 mmol) in THF (10 mL) was added DIAD (0.47 mL, 2.4 mmol) at 0° C. After 10 min, (1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-3-hydroxy-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (0.93 mL, 2.2 mmol) was added as solid. After 5 min, sodium thiomethoxide (180 mg, 2.6 mmol) was added. After 20 min, the cold bath was removed and the mixture was stirred at room temperature for 1.5 hrs. To the mixture was added water (15 mL), methanol (15 mL), and oxone (5.4 g, 8.8 mmol) and kept for 16 h. The mixture was extracted with methylene chloride (100 mL) and water (50 mL). The organic layer was dried over MgSO4. The solvent was removed in vacuo to give a solid. The solid was purified with prep HPLC to give (1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-3-methanesulfonyl-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (50 mg, 5% yield): mp, 148–150° C.; 1H NMR (CDCl3) δ 0.89–0.94 (m, 2H, CH2), 1.10–1.13 (m, 2H, CH2), 1.46 (t, J=7 Hz, 3H, CH3), 1.65–1.73 (m, 1H, CH), 2.60–2.69 (m, 2H, CH2), 2.96 (s, 3H, CH3), 3.02–3.22 (m, 2H, CH2), 3.87 (s, 3H, CH3), 3.99 (d, J=17 Hz, 1H, NCHH), 4.07 (q, J=7 Hz, 2H, CH2), 4.30 (d, J=17 Hz, 1H, NCHH), 5.48 (t, J=8 Hz, 1H, NCH), 6.84–7.02 (m, 4H, Ar), 7.46 (t, J=8 Hz, 1H, Ar), 8.45 (d, J=8 Hz, 1H, Ar), 10.49 (s, 1H, NH); 13C NMR (CDCl3) δ 8.30, 14.75, 16.19, 23.78, 41.24, 45.95, 51.99, 53.01, 56.00, 64.65, 111.60, 112.37, 116.88, 117.00, 117.89, 119.46, 129.82, 133.52, 138.09, 141.29, 148.87, 149.55, 169.79, 172.66; Anal Calcd for C25H30N2O6S1: C, 61.71; H, 6.21; N, 5.76. Found: C, 61.33; H, 6.19; N, 5.59.

후처리

  1. waitAfter 5 min
  2. waitAfter 20 min
  3. customthe cold bath was removed
  4. waitkept for 16 h
  5. extractionThe mixture was extracted with methylene chloride (100 mL) and water (50 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. customThe solvent was removed in vacuo
  8. customto give a solid
  9. customThe solid was purified with prep HPLC

출처 및 근거

ORD 기록
ord-1bc993bd044c43828823666da153d5d3
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07034052B2

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