Lithium Chloride → 1,1'-[[(Propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(2,2,2-trichloroethoxycarbonyl)-11-(tert-butyldimethylsilyloxy)-7-methoxy-2-ethynylphenyl-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]]

HRID 18864

반응식

HRID 18864 반응식
[CH2:1]([O:46][CH:47]1[C@H:51]2[C@H:52]([O:72][Si:73]([C:76]([CH3:79])([CH3:78])[CH3:77])([CH3:75])[CH3:74])[N:53]([C:64]([O:66][CH2:67][C:68]([Cl:71])([Cl:70])[Cl:69])=[O:65])[C:54]3[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][C:55]=3[C:56](=[O:57])[N:50]2[CH:49]=[C:48]1OS(C(F)(F)F)(=O)=O)[CH2:2][CH2:3][O:4][CH:5]1[C@H:9]2[C@H:10]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[N:11]([C:22]([O:24][CH2:25][C:26]([Cl:29])(Cl)[Cl:27])=[O:23])[C:12]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:13]=3[C:14](=[O:15])[N:8]2[CH:7]=[C:6]1OS(C(F)(F)F)(=O)=O.[Li+].[Cl-:89].C([Sn](CCCC)(CCCC)[C:95]#[C:96][C:97]1[CH:102]=[CH:101][CH:100]=[CH:99][CH:98]=1)CCC>C1COCC1.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>[CH2:1]([O:46][C:47]1([C:102]2[CH:101]=[CH:100][CH:99]=[CH:98][C:97]=2[C:96]#[CH:95])[C@H:51]2[C@H:52]([O:72][Si:73]([C:76]([CH3:78])([CH3:77])[CH3:79])([CH3:74])[CH3:75])[N:53]([C:64]([O:66][CH2:67][C:68]([Cl:69])([Cl:71])[Cl:70])=[O:65])[C:54]3[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][C:55]=3[C:56](=[O:57])[N:50]2[CH:49]=[CH:48]1)[CH2:2][CH2:3][O:4][C:5]1([C:98]2[CH:99]=[CH:100][CH:101]=[CH:102][C:97]=2[C:96]#[CH:95])[C@H:9]2[C@H:10]([O:30][Si:31]([C:34]([CH3:37])([CH3:35])[CH3:36])([CH3:33])[CH3:32])[N:11]([C:22]([O:24][CH2:25][C:26]([Cl:27])([Cl:29])[Cl:89])=[O:23])[C:12]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:13]=3[C:14](=[O:15])[N:8]2[CH:7]=[CH:6]1

참가 물질

6

반응물 3

HCID 433294Lithium ChlorideHCID 630640Tributyl(2-phenylethynyl)stannaneHCID 1317281911,1'-[[(Propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(2,2,2-trichloroethoxycarbonyl)-11-(tert-butyldimethylsilyloxy)-7-methoxy-2-[[(trifluoromethyl)sulfonyl]oxy]-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]]

생성물 1

HCID 1317281921,1'-[[(Propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(2,2,2-trichloroethoxycarbonyl)-11-(tert-butyldimethylsilyloxy)-7-methoxy-2-ethynylphenyl-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]]수율 92.7%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

A catalytic amount of Pd(PPh3)4 was added to a stirred mixture of triflate 13 (193 mg, 0.13 mmol), LiCl (34 mg, 0.80 mmol, 6.0 eq) and tributyl(phenylethynyl)tin (0.14 mL, 157 mg, 0.40 mmol, 3.0 eq) in dry THF (5 mL). The reaction mixture was heated at reflux for 2.5 h when TLC showed the complete consumption of the starting material. After cooling to room temperature, excess solvent was removed and the residue was dissolved in DCM (20 mL), followed by washing with 10% NH4OH (20 mL). The aqueous layer was extracted with DCM (3×20 mL), and the organic extracts were combined, washed with brine (50 mL) and dried (MgSO4). Filtration and evaporation of solvent afforded the crude product which was purified by flash column chromatography (80:20 v/v hexane/EtOAc) to afford 17 as a yellow glass (162 mg, 90%): 1H NMR (400 MHz, CDCl3) δ 7.40-7.37 (m, 4H, H15), 7.26-7.19 (m, 10H, H3, H6, H16 and H17), 6.70 (s, 2H, H9), 5.85 (d, 2H, J=8.8 Hz, H11), 5.15 (d, 2H, J=12.0 Hz, Troc CH2), 4.24-4.19 (m, 2H, OCH2CH2CH2O), 4.12-4.02 (m, 4H, Troc CH2 and OCH2CH2CH2O), 3.86-3.79 (m, 8H, OCH3×2 and H11a), 3.15 (dd, 2H, J=10.8, 16.5 Hz, H1), 2.63 (d, 2H, J=16.5 Hz, H1), 2.37-2.35 (m, 2H, OCH2CH2CH2O), 0.82 (s, 18H, TBS CH3×6), 0.22 and 0.18 (s×2, 12H, TBS CH3×4); 13C NMR (100.6 MHz, CDCl3) δ 163.8 (Cquat), 153.6 (Cquat), 150.8 (Cquat), 149.3 (Cquat), 133.3 (C3), 131.4 (C15), 128.4 (C16 and C17), 127.8 (Cquat), 125.1 (Cquat), 123.0 (Cquat), 114.0 (C6), 110.0 (C9), 104.8 (Cquat), 95.2 (Troc CCl3), 93.7 (Calkyne), 86.9 (C11), 83.6 (Calkyne), 74.8 (Troc CH2), 66.0 (OCH2CH2CH2O), 61.4 (C11a), 56.2 (OCH3), 37.8 (C1), 28.8 (OCH2CH2CH2O), 25.6 (TBS CH3), 17.8 (TBS Cquat); MS (ES), m/z (relative intensity) 1344 (M+., 8), 625 (100).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2.5 h when TLC
  3. customthe complete consumption of the starting material
  4. customexcess solvent was removed
  5. dissolutionthe residue was dissolved in DCM (20 mL)
  6. washby washing with 10% NH4OH (20 mL)
  7. extractionThe aqueous layer was extracted with DCM (3×20 mL)
  8. washwashed with brine (50 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationFiltration and evaporation of solvent
  11. customafforded the crude product which
  12. customwas purified by flash column chromatography (80:20 v/v hexane/EtOAc)

출처 및 근거

ORD 기록
ord-70a15ae2f5494d6e8d04e4f7cad1a8a8
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741319B2

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