HCID 58765273, compound → HCID 16072810, compound

HRID 1394852Notes

Reaction equation

HRID 1394852 reaction equation
[CH3:1][C:2]([CH3:35])([O:4][C:5]([N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]2=[C:18]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)[C:19]3[CH:20]=[CH:21][C:22]([C:25]([O:27]C)=[O:26])=[CH:23][C:24]=3[N:10]2[CH2:9][CH2:8]1)=[O:6])[CH3:3]>CO.C1COCC1.[OH-].[Na+]>[CH3:3][C:2]([CH3:35])([O:4][C:5]([N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]2=[C:18]([CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)[C:19]3[CH:20]=[CH:21][C:22]([C:25]([OH:27])=[O:26])=[CH:23][C:24]=3[N:10]2[CH2:9][CH2:8]1)=[O:6])[CH3:1]

Participants

5

Reactant 1

HCID 58765273HCID 58765273, compound

Product 1

HCID 16072810HCID 16072810, compoundYield 96.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of methyl 5-[(1,1-dimethylethoxy)carbonyl]-13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-carboxylate (1.08 g, 2.28 mmol) in MeOH (40 mL), THF (30 mL) and 5N aqueous NaOH (2 mL) was heated at 50° C. overnight. Additional 10N aqueous NaOH (6 mL) was added and the reaction mixture was again heated at 50° C. for 5 h. The reaction was cooled, concentrated under vacuum and partitioned between EtOAc (60 mL) and ½ saturated aqueous NH4Cl (30 mL). The organic layer was washed with brine (10 mL) and the combined aqueous layers were extracted with EtOAc (40 mL). The combined organic layers were dried (MgSO4), filtered, concentrated to yield 5-[(1,1-dimethylethoxy)carbonyl]-13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-carboxylic acid (1.01 g, 2.20 mmol, 96%) as a yellow solid. 1HNMR (500 MHz, Acetone-d6) δ 8.23 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.60-7.51 (m, 3H), 7.48-7.41 (m, 1H), 4.81 (br s, 1H), 4.66 (br s, 1H), 3.86 (br s, 1H), 3.59 (br s, 1H), 3.12-2.97 (m, 1H), 2.15-1.67 (m, 6H), 1.52-1.20 (m, 4H), 1.18 (s, 9H). LCMS: m/e 461 (M+H)+, ret time 2.26 min, column C, 2 minute gradient, start at 0% B.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated under vacuum
  3. custompartitioned between EtOAc (60 mL) and ½ saturated aqueous NH4Cl (30 mL)
  4. washThe organic layer was washed with brine (10 mL)
  5. extractionthe combined aqueous layers were extracted with EtOAc (40 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-415694a24c9b4aceb04a94081fd5bc57
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

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