Sodium Hydroxide → HCID 66608384, compound

HRID 469682Notes

Reaction equation

HRID 469682 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:23]=[C:22]3[C:18]([C:19]4[CH:38]5[NH:39][CH:35]([CH2:36][CH2:37]5)[CH2:34][C:20]=4[N:21]3S(C3C=CC(C)=CC=3)(=O)=O)=[CH:17][CH:16]=2)[C:11](=[O:40])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].CO.C(Cl)[Cl:46]>O>[ClH:46].[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:23]=[C:22]3[C:18]([C:19]4[CH:38]5[NH:39][CH:35]([CH2:36][CH2:37]5)[CH2:34][C:20]=4[NH:21]3)=[CH:17][CH:16]=2)[C:11](=[O:40])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226129Dichloromethane methanolHCID 58092224HCID 58092224, compound

Product 1

HCID 66608384HCID 66608384, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-(Benzyloxy)-1-(5-tosyl-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indol-3-yl)pyridin-2(1H)-one (130 mg, 0.24 mmol) and NaOH (594 mg, 14.8 mmol) were added to 1:1 MeOH/CH2Cl2 (20 mL) under N2, and the resulting suspension was stirred at reflux for 16 h. The reaction was cooled, H2O was added, and the resulting suspension was filtered. The obtained solid was purified by flash chromatography (silica gel, CH2Cl2/(9:1 MeOH/NH4OH), 100:0 to 80:20) afforded the free-base that was subsequently converted to the hydrochloride salt according to the procedure for Example 2 (step d) to provide the title compound (41 mg, 39%) as a white solid: mp 209-214° C.; 1H NMR (300 MHz, DMSO-d6) δ 11.39 (s, 1H), 9.54 (br s, 1H), 9.14 (d, J=9.8 Hz, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.55 (d, J=7.6 Hz, 1H), 7.48-7.44 (m, 2H), 7.44-7.40 (m, 2H), 7.37 (dd, J=8.0, 8.0 Hz, 1H), 7.29 (d, J=1.8 Hz, 1H), 6.95-6.93 (dd, J=8.3, 1.8 Hz, 1H), 6.09-6.07 (dd, J=7.6, 2.6 Hz, 1H), 5.96 (d, J=2.7 Hz, 1H), 5.18 (br s, 1H), 5.14 (s, 2H), 4.40 (br m, 1H), 3.44-3.40 (dd, J=17.0, 4.0 Hz, 1H), 2.90 (d, J=17.0 Hz, 1H), 2.29-2.26 (m, 2H), 2.07-2.04 (m, 1H), 1.80-1.75 (m, 1H); ESI MS m/z 398 [M+H]+; HPLC (Method B)>99% (AUC), tR=12.7 min.

Workup

  1. temperatureat reflux for 16 h
  2. temperatureThe reaction was cooled
  3. filtrationthe resulting suspension was filtered
  4. customThe obtained solid was purified by flash chromatography (silica gel, CH2Cl2/(9:1 MeOH/NH4OH), 100:0 to 80:20)
  5. customafforded the free-base that

Sources & evidence

ORD record
ord-272a9fc858ea482ba8c9608aab43e8a7
Source dataset
uspto-grants-2014_01
Patent number
US08629158B2

Reaction notes

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