Cesium carbonate → 6-Carbomethoxy-13-cyclohexyl-N-[(dimethylamino)sulfonyl]-5H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 860737Notes

Reaction equation

HRID 860737 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([NH:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[O:17])=[CH:13][CH:14]=3)[NH:9][C:8]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2C=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.COP([C:39](=[CH2:44])[C:40]([O:42][CH3:43])=[O:41])(OC)=O.[C:45]([O-])([O-])=O.[Cs+].[Cs+].C([O-])(=O)C=C>CN(C=O)C.C(OCC)(=O)C>[C:40]([C:39]1[CH2:44][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:8]2=[C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[C:15]3[CH:14]=[CH:13][C:12]([C:16]([NH:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[O:17])=[CH:11][C:10]=3[N:9]2[CH:45]=1)([O:42][CH3:43])=[O:41]

Participants

7

Reactant 4

HCID 10796Cesium carbonate2×HCID 25188AcrylateHCID 3016938Methyl 2-(dimethoxyphosphinyl)acrylateHCID 587651853-cyclohexyl-N-[(dimethylamino)sulfonyl]-2-(2-formylphenyl)-1H-indole-6-carboxamide

Product 1

HCID 688586576-Carbomethoxy-13-cyclohexyl-N-[(dimethylamino)sulfonyl]-5H-indolo[2,1-a][2]benzazepine-10-carboxamideYield 59%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-cyclohexyl-N-[(dimethylamino)sulfonyl]-2-(2-formylphenyl)-1H-indole-6-carboxamide (1.06 g, 2.1 mmol), methyl 2-(dimethoxyphosphoryl)acrylate (0.4 mL, 3.2 mmol), and Cs2CO3 (1.04 g, 3.2 mmol) in DMF (4 mL) was stirred at 60° C. for 18 hr, at which time additional Cs2CO3 4 g, 0.32 mmol) and methyl dimethoxyphosphoryl)acrylate (0.4 mL, 3.2 mmol) were added. The mixture was stirred for an additional 8 hr, cooled and diluted with ethyl acetate. The resulting mixture was washed with dilute HCl (3×) followed by brine (3×). The solution was concentrated to leave the crude product as a yellow solid (1.2 g). The crude product was purified utilizing a Biotage apparatus with a prepacked silicic acid column and using gradients of hexanes: ethyl acetate:acetic acid of from (100:2:.0.5) to (64:36:0.5). The product containing fractions were combined and concentrated to dryness to afford the titled compound as a pale yellow solid (640 mg, 59%). MS m/z 522 (MH+).

Workup

  1. additionwere added
  2. temperaturecooled
  3. washThe resulting mixture was washed with dilute HCl (3×)
  4. concentrationThe solution was concentrated
  5. customto leave the crude product as a yellow solid (1.2 g)
  6. customThe crude product was purified
  7. additionThe product containing fractions
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-c96e652dd58a42ebad25f4613352e172
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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