Sodium Hydroxide → HCID 66873343, compound

HRID 474925Notes

Reaction equation

HRID 474925 reaction equation
[OH-:1].[Na+].S([N:13]1[C:21]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:15]2[CH2:22][N:23](C([O-])=O)[CH2:24][CH2:25][CH2:26][C:14]1=2)(C1C=CC(C)=CC=1)(=O)=O.C(Cl)[Cl:31].[CH3:33][OH:34]>O>[ClH:31].[CH2:15]([O:1][C:25]1[CH:26]=[CH:14][N:13]([C:19]2[CH:18]=[CH:17][C:16]3[C:15]4[CH2:22][NH:23][CH2:24][CH2:25][CH2:26][C:14]=4[NH:13][C:21]=3[CH:20]=2)[C:33](=[O:34])[CH:24]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226129Dichloromethane methanolHCID 86649546HCID 86649546, compound

Product 1

HCID 66873343HCID 66873343, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

NaOH (0.44 g, 11 mmol) was added to a solution of tert-butyl 8-(4-benzyloxy)-2-oxopyridin-1(2H)-yl)-6-tosyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylate (0.14 g, 0.22 mmol) in 1:1 CH2Cl2/MeOH (20 mL), and the resulting solution was heated at reflux for 18 h. The mixture was diluted with H2O and was extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to dryness. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 25:75 over 20 column volumes and held for 2 column volumes) provided the title compound (58 mg, 55%) as a yellow film: 1H NMR (500 MHz, DMSO-d6) δ 11.08-11.05 (m, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.48-7.35 (m, 6H), 7.19 (s, 1H), 6.87 (d, J=8.0 Hz, 1H), 6.06 (dd, J=7.0, 2.0 Hz, 1H), 5.95 (d, J=2.5 Hz, 1H), 5.14 (s, 2H), 4.55 (s, 2H), 3.65 (t, J=5.0 Hz, 2H), 2.94 (t, J=5.5 Hz, 2H), 1.83-1.80 (m, 2H), 1.35-1.28 (m, 9H).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureat reflux for 18 h
  3. extractionwas extracted with CH2Cl2 (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated under reduced pressure to dryness
  6. temperatureFlash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 25:75 over 20 column volumes and held for 2 column volumes)

Sources & evidence

ORD record
ord-331c37dd7c6649aa81615eb2c41215d1
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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