Dimethyl Sulfoxide → HCID 178491571, 화합물

HRID 350524노트

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HRID 350524 반응식
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH2:30][C:31]([N:33]2[CH2:37][CH2:36][CH2:35][CH:34]2[CH2:38]O)=[O:32])[CH:16]=[CH:17][C:18]=1[NH:19][C:20]([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])=[O:21].C(N(CC)CC)C.[NH2:47][C@@H:48]1[CH2:53][CH2:52][C@H:51]([C:54]([O:56][CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)=[O:55])[CH2:50][CH2:49]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.ClCCCl.CC(O)=O.O>[CH2:57]([O:56][C:54]([C@H:51]1[CH2:52][CH2:53][C@@H:48]([NH:47][CH2:38][CH:34]2[CH2:35][CH2:36][CH2:37][N:33]2[C:31](=[O:32])[CH2:30][C:15]2[CH:16]=[CH:17][C:18]([NH:19][C:20]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH3:29])=[O:21])=[C:13]([O:12][CH3:11])[CH:14]=2)[CH2:49][CH2:50]1)=[O:55])[C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1

참가 물질

11

반응물 6

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 693335311-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinemethanolHCID 178511568HCID 178511568, 화합물

생성물 1

HCID 178491571HCID 178491571, 화합물수율 83%

시약·촉매·용매 4

HCID 111,2-Dichloroethane용매HCID 176Acetic Acid용매HCID 962Water용매HCID 6344Dichloromethane용매2회

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온도
-78 °C

실험 절차

To a stirred solution of oxalyl chloride (0.3 ml, 3.3 mmol) in CH2Cl2 (30.0 ml) was added DMSO (6.6 ml, 0.51 mmol) at −78° C. After 5 minutes, to the mixture was added 1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinemethanol (1.2 g, 3.0 mmol) in CH2Cl2 (5.0 ml). The mixture was stirred for 30 minutes at −78° C., and triethylamine (2.1 ml, 15.0 mmol) was added. The mixture was stirred for 30 minutes at −78° C., and stirred for 30 minutes at room temperature. Water was added to the mixture, and extracted with CH2Cl2. The extract was washed with water, then dried over Na2SO4, and concentrated in vacuo. The crude product was used to the subsequent reaction without further purification. To a stirred solution of the crude product, benzyl cis-4-aminocyclohexanecarboxylate (769 mg, 3.3 mmol), and AcOH (0.32 ml) in DCE (10 ml) was added NaBH(OAc)3 (1.1 g, 5.4 mmol) at 0° C. The reaction mixture was stirred at room temperature for 18 hr. The mixture was concentrated in vacuo. Sat. NaHCO3 was added to the residue, and extracted with CH2Cl2. The extract was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel with MeOH—CH2Cl2 (1:9, v/v) as eluent to give benzylcis-4-[[1-[3-methoxy-4-[N′-(2-methylphenyl) ureido]phenylacetyl]-2-pyrrolidinyl]methylamino]cyclohexanecarboxylate (1.5 g, 83%) as an amorphous solid. 1H-NMR (CDCl3) δ 1.40–1.65 (m, 6H), 1.80–1.98 (m, 6H), 2.26 (s, 3H), 2.45–2.65 (m, 3H), 2.81–2.86 (m, 1H), 3.44–3.46 (m, 2H), 3.56 (s, 2H), 3.67 (s, 3H), 3.90–4.15 (m, 1H), 5.09 and 5.11 (each s, total 2H), 6.74–6.83 (m, 3H), 7.07–7.20 (m, 4H), 7.31–7.35 (m, 5H), 7.53–7.55 (m, 1H), 8.02–8.06 (m, 1H).

후처리

  1. stirringThe mixture was stirred for 30 minutes at −78° C.
  2. stirringstirred for 30 minutes at room temperature
  3. extractionextracted with CH2Cl2
  4. washThe extract was washed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was used to the subsequent reaction without further purification
  8. stirringThe reaction mixture was stirred at room temperature for 18 hr
  9. concentrationThe mixture was concentrated in vacuo
  10. additionSat. NaHCO3 was added to the residue
  11. extractionextracted with CH2Cl2
  12. washThe extract was washed with brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by column chromatography on silica gel with MeOH—CH2Cl2 (1:9, v/v) as eluent

출처 및 근거

ORD 기록
ord-6243ab6aa2364efd936336abed65c81b
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07179819B2

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