5-(4-Fluorophenyl)cyclohexane-1,3-dione → 4-[(3aS)-6-(4-Fluorophenyl)-8,10-dioxo-2,3,3a,5,6,7,8,10-octahydro-1H-pyrrolizino[1,2-b]quinolin-9-yl]-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamide

HRID 458442Notes

Reaction equation

HRID 458442 reaction equation
C(C1[C:16]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22](F)=[CH:21][CH:20]=2)=[N:15]C2[C@H]3N(C(=O)C=2C=1C1C=CC(C(NCC2OC=CC=2)=O)=CC=1)CCC3)(=O)C.[F:41][C:42]1[CH:47]=[CH:46][C:45]([CH:48]2[CH2:57][C:56]3[N:55]=[C:54]4[C@H:58]5[N:62]([C:63](=[O:64])[C:53]4=[C:52]([C:65]4[CH:73]=[CH:72][C:68]([C:69](O)=[O:70])=[CH:67][CH:66]=4)[C:51]=3[C:50](=[O:74])[CH2:49]2)[CH2:61][CH2:60][CH2:59]5)=[CH:44][CH:43]=1.FC1C=CC(C2CC(=O)CC(=O)C2)=CC=1.C(OC(N1CCCC1C(=O)/C(/C(OCC)=O)=C/C1C=CC(C(O)=O)=CC=1)=O)(C)(C)C>>[F:41][C:42]1[CH:47]=[CH:46][C:45]([CH:48]2[CH2:57][C:56]3[N:55]=[C:54]4[C@H:58]5[N:62]([C:63](=[O:64])[C:53]4=[C:52]([C:65]4[CH:73]=[CH:72][C:68]([C:69]([NH:15][C@H:16]6[C:20]7[C:19](=[CH:24][CH:23]=[CH:22][CH:21]=7)[CH2:18][CH2:17]6)=[O:70])=[CH:67][CH:66]=4)[C:51]=3[C:50](=[O:74])[CH2:49]2)[CH2:61][CH2:60][CH2:59]5)=[CH:44][CH:43]=1

Participants

5

Reactant 4

HCID 7301365-(4-Fluorophenyl)cyclohexane-1,3-dioneHCID 184419324-[(1Z)-3-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]-2-(ethoxy-carbonyl)-3-oxo-1-propenyl]benzoic acidHCID 695162694-[(3aS)-6-(4-fluorophenyl)-8,10-dioxo-2,3,3a,5,6,7,8,10-octahydro-1H-pyrrolizino[1,2-b]quinolin-9-yl]benzoic acidHCID 697426234-{(9aS)-3-acetyl-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4-yl}-N-(2-furylmethyl)benzamide

Product 1

HCID 695173114-[(3aS)-6-(4-Fluorophenyl)-8,10-dioxo-2,3,3a,5,6,7,8,10-octahydro-1H-pyrrolizino[1,2-b]quinolin-9-yl]-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamideYield 52%

Procedure

Using the synthetic method described earlier in the synthesis of 4-{(9aS)-3-acetyl-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl}-N-(2-furylmethyl)benzamide (Example 29), the title compound was prepared from 4-[(3aS)-6-(4-fluorophenyl)-8,10-dioxo-2,3,3a,5,6,7,8,10-octahydro-1H-pyrrolizino[1,2-b]quinolin-9-yl]benzoic acid (prepared using the enamine of 5-(4-fluorophenyl)-1,3-cyclohexanedione and Knoevenagel product 4-[(1Z)-3-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]-2-(ethoxy-carbonyl)-3-oxo-1-propenyl]benzoic acid). A portion of the crude material (100 mg) was chromatographed (silica gel/ethyl acetate) to give the title compound as a tan powder (52 mg, 52%). LCMS m/z 572 (MH+) 1H NMR (300 MHz, DMSO-d6) δ 7.90 (d, 2H), 7.40 (m, 2H), 7.10–7.35 (m, 6H), 7.10 (dd, 2H), 6.40 (d, 1H), 5.75 (m, 2H), 4.75 (d, 1H), 3.30–3.75 (m, 2H), 2.80–3.10 (m, 2H), 2.70 (m, 1H), 2.55 (m, 1H), 2.35 (m, 1H), 1.95 (m, 1H), 1.75 (m, 4H), 1.50 (m, 2H) ppm.

Workup

  1. customprepared
  2. customA portion of the crude material (100 mg) was chromatographed (silica gel/ethyl acetate)

Sources & evidence

ORD record
ord-bb16498b4f444329b5f7cb324a230f1b
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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