Dichloromethane → HCID 66603557, compound

HRID 1918496Notes

Reaction equation

HRID 1918496 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:20]=[C:19]3[N:21](S(C4C=CC(C)=CC=4)(=O)=O)[C:22]4[CH2:23][CH:24]5[N:29]([CH2:30][C:31]=4[C:18]3=[CH:17][CH:16]=2)[CH2:28][CH2:27][CH2:26][CH2:25]5)[C:11](=[O:42])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].C(Cl)[Cl:46]>CO>[ClH:46].[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:20]=[C:19]3[NH:21][C:22]4[CH2:23][CH:24]5[N:29]([CH2:30][C:31]=4[C:18]3=[CH:17][CH:16]=2)[CH2:28][CH2:27][CH2:26][CH2:25]5)[C:11](=[O:42])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 58092297HCID 58092297, compound

Product 1

HCID 66603557HCID 66603557, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-(benzyloxy)-1-(5-tosyl-5,6,6a,7,8,9,10,12-octahydroindolo[2,3-b]quinolizin-3-yl)-pyridin-2(1H)-one (50 mg, 0.086 mmol) in CH3OH (2 mL) and CH2Cl2 (2 mL) was added NaOH (17 mg, 0.43 mmol). The mixture was stirred at room temperature until complete. The mixture was filtered through a layer of Celite; the filtrate was concentrated; and the resulting oil was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give the free base of the title compound (29 mg, 79%) as a yellow solid. The yellow solid was dissolved in CH3OH (2 mL) and treated with 2 N HCl in Et2O (1 mL). The resulting solid was isolated by filtration and dried under vacuum to give the title compound (18 mg, 57%) as a yellow powder: mp 270-273° C.; 1H NMR (500 MHz, CD3OD) δ 7.59 (d, J=8.0 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.48-7.35 (m, 6H), 7.03 (dd, J=8.5, 1.5 Hz, 1H), 6.32 (dd, J=7.5, 3.0 Hz, 1H), 6.15 (d, J=2.5 Hz, 1H), 5.19 (s, 2H), 4.74 (d, J=14.5 Hz, 1H), 4.36 (d, J=14.5 Hz, 1H), 3.79 (d, J=13.0 Hz, 1H), 3.69-3.67 (m, 1H), 3.30-3.28 (m, 2H), 3.03 (dd, J=16.5, 10.5 Hz, 1H), 2.36-2.30 (m, 1H), 2.08-1.97 (m, 2H), 1.88-1.70 (m, 3H); ESI MS m/z 426 [M+H]+; HPLC (Method A) 98.5% (AUC), tR=12.99 min.

Workup

  1. filtrationThe mixture was filtered through a layer of Celite
  2. concentrationthe filtrate was concentrated
  3. customand the resulting oil was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-4de4dcaca0a34be1bc82a10d6d1f98c5
Source dataset
uspto-grants-2013_12
Patent number
US08618299B2

Reaction notes

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