Lithium diisopropylamide → tert-butyl 4-((6-cyanobenzofuran-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174090노트

반응식

HRID 2174090 반응식
[O:1]1[C:5]2[CH:6]=[C:7]([C:10]#[N:11])[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[Li+].CC([N-]C(C)C)C.[CH:20]([C:22]1[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]2[C:23]=1[CH:24]=[CH:25][N:26]2[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[O:21]>C1COCC1.CO.[NH4+].[Cl-].[Cl-].[Na+].O.CCOC(C)=O>[C:10]([C:7]1[CH:8]=[CH:9][C:4]2[CH:3]=[C:2]([CH:20]([OH:21])[C:22]3[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4[C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[O:1][C:5]=2[CH:6]=1)#[N:11]

참가 물질

9

반응물 3

HCID 2724682Lithium diisopropylamideHCID 212514851-Benzofuran-6-carbonitrileHCID 72191522tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate

생성물 1

HCID 86701726tert-butyl 4-((6-cyanobenzofuran-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

시약·촉매·용매 5

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매HCID 25517Ammonium Chloride용매HCID 57417360Sodium chloride; water용매

실험 절차

To a solution of benzofuran-6-carbonitrile (CAS #: 17450-68-9) (29.7 mg, 0.207 mmol) in THF (1.7 mL), 1.8M LDA (heptane/THF/ethylbenzene, 0.125 mL, 0.225 mmol) was added at −78° C. After stirring for 30 min., a solution of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (50 mg, 0.173 mmol) in THF (1.0 mL) was added to the reaction mixture at the same temperature. After stirring for 5 minutes the reaction mixture was diluted with MeOH (1 mL), sat. aq. NH4Cl (5 mL), brine (5 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash column chromatography to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.07 (s, 1H) 7.68-7.80 (m, 1H) 7.60 (dd, J=8.08, 1.52 Hz, 1H) 7.52 (d, J=3.79 Hz, 1H) 6.91 (s, 1H) 6.72-6.86 (m, 2H) 6.49 (dd, J=4.80, 1.01 Hz, 1H) 6.32 (d, J=5.05 Hz, 1H) 3.85 (s, 3H) 2.53 (s, 3H) 1.51-1.61 (m, 9H).

후처리

  1. stirringAfter stirring for 5 minutes the reaction mixture
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-5b075f8a6cc64c7a807d620006bd02d4
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056874B2

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