Hydrochloric Acid → 5-(10-(Tert-butoxycarbonyl)-13-cyclohexyl-3-methoxy-7h-indolo[2,1-a][2]benzazepin-6-yl)-1,3-oxazole-4-carboxylic acid

HRID 1994089Notes

Reaction equation

HRID 1994089 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:25][CH:24]=[N:23][C:22]=4[C:26]([O:28]C)=[O:27])=[CH:18][C:17]4[CH:30]=[C:31]([O:34][CH3:35])[CH:32]=[CH:33][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.P([O-])(O)(O)=O.[Na+].Cl>C1COCC1>[C:39]([O:38][C:36]([C:11]1[CH:10]=[CH:9][C:8]2[C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:15]3[C:16]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:17]=4[CH:18]=[C:19]([C:21]4[O:25][CH:24]=[N:23][C:22]=4[C:26]([OH:28])=[O:27])[CH2:20][N:14]3[C:13]=2[CH:12]=1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2723671Tetrabutylammonium HydroxideHCID 23672064Monosodium phosphateHCID 25211328Tert-butyl 13-cyclohexyl-3-methoxy-6-(4-(methoxycarbonyl)-1,3-oxazol-5-yl)-7h-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 591337975-(10-(Tert-butoxycarbonyl)-13-cyclohexyl-3-methoxy-7h-indolo[2,1-a][2]benzazepin-6-yl)-1,3-oxazole-4-carboxylic acidYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 13-cyclohexyl-3-methoxy-6-(4-(methoxycarbonyl)-1,3-oxazol-5-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate (205 mg, 0.360 mmol) was dissolved in THF (3.0 ml) and tetrabutylammonium hydroxide (1.1 mL, 1.100 mmol) (1.0M in methanol) was added to the reaction. The reaction was capped and stirred at room temperature for 2 hrs. A 0.1M aqueous solution of NaH2PO4 was added to the reaction followed by 0.1N aqueous hydrochloric acid. The product was extracted into ethyl acetate and the organic phase washed sequentially with 0.1N aqueous hydrochloric acid, 0.1M aqueous NaH2PO4, brine and dried over magnesium sulfate. The product solution was filtered, solvent removed and product dried in vacuuo to yield 191 mg of a yellow solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 0.77-0.94 (m, 1H) 1.12-1.31 (m, 3H) 1.30-1.59 (m, 5H) 1.62 (s, 9H) 1.76 (d, J=11.29 Hz, 2H) 1.87-2.18 (m, 4H) 2.76-2.90 (m, 1H) 3.91 (s, 3H) 4.45 (d, J=14.04 Hz, 1H) 6.03 (d, J=12.21 Hz, 1H) 7.03 (d, J=2.44 Hz, 1H) 7.08 (dd, J=8.55, 2.75 Hz, 1H) 7.53 (d, J=8.85 Hz, 1H) 7.68 (d, J=8.24 Hz, 1H) 7.82 (d, J=8.55 Hz, 1H) 7.91 (s, 1H) 8.21 (d, J=5.80 Hz, 2H). LC-MS retention time 1.86 min; m/z 553 (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Xterra MS 7u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customThe reaction was capped
  2. extractionThe product was extracted into ethyl acetate
  3. washthe organic phase washed sequentially with 0.1N aqueous hydrochloric acid, 0.1M aqueous NaH2PO4, brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe product solution was filtered
  6. customsolvent removed
  7. customproduct dried in vacuuo

Sources & evidence

ORD record
ord-200b7df3c57f4fce822c0ea57a4fe50c
Source dataset
uspto-grants-2010_01
Patent number
US07652004B2

Reaction notes

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