Ammonia → 6-(aminocarbonyl)-13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, methyl ester

HRID 273350Notes

Reaction equation

HRID 273350 reaction equation
[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][C:7]([C:22](O)=[O:23])=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:25]CN(C(C)C)C(C)C.CN(C(ON1N=N[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH3:56].Cl>CN(C=O)C>[NH2:56][C:22]([C:7]1[CH2:8][N:9]2[C:18]3[CH:17]=[C:16]([C:19]([O:21][CH3:25])=[O:20])[CH:15]=[CH:14][C:13]=3[C:12]([CH:43]3[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)=[C:10]2[C:11]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH:6]=1)=[O:23]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 665887027H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid

Product 1

HCID 589406746-(aminocarbonyl)-13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, methyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22 °C

Procedure

To a solution of 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid, 13-cyclohexyl-, 10-methyl ester (1.10 g, 2.65 mmol) in DMF (7.0 mL) and DIPEA (1.85 mL, 10.6 mmol) was added TBTU (1.28 g, 3.97 mmol). The resulting solution was stirred at 22° C. for 15 min. Ammonia (0.5M in dioxane, 21.2 mL, 10.6 mmol) was added and this solution was stirred at 22° C. for 18 hr. 1M HCl (50 mL) was added and the aqueous layer was extracted with CHCl3 (2×50 mL). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. Silica gel chromatography (4:1 EtOAc:hexanes) of the concentrate afforded the title compound (900 mg, 82%) as a yellow oil. MS m/z 415 (MH+), 1H NMR (300 MHz, CDCl3) δ ppm 1.17-1.69 (m, 5H), 1.79 (m, 2H), 1.87-2.16 (m, 3H), 2.86 (m, 1 H), 3.94 (s, 3H), 4.14 (broad m, 1 H), 5.72 (broad m, 1 H), 7.38 (s, 1 H), 7.46 (m, 2 H), 7.53 (dd, J=7.6, 8.4 Hz, 1 H), 7.61 (d, J=7.6 Hz, 1 H), 7.74 (d, J=8.4 Hz, 1 H), 7.87 (d, J=8.4 Hz, 1 H), 8.29 (s, 1 H).

Workup

  1. stirringthis solution was stirred at 22° C. for 18 hr
  2. extractionthe aqueous layer was extracted with CHCl3 (2×50 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-db77ebcdb67d410f9afc935c3f6a7b54
Source dataset
uspto-grants-2008_11
Patent number
US07456165B2

Reaction notes

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