Hydrochloric Acid → 4-(benzyloxy)-1-(5-(ethoxymethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one

HRID 930738Notes

Reaction equation

HRID 930738 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28][C:20]=4[N:21]([CH2:24][O:25][CH2:26][CH3:27])[C:22]=3[CH:23]=2)[C:11](=[O:39])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CCO.CCOCC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:31][NH:30][CH2:29][CH2:28][C:20]=4[N:21]([CH2:24][O:25][CH2:26][CH3:27])[C:22]=3[CH:23]=2)[C:11](=[O:39])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57950438tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-(ethoxymethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Product 1

HCID 441944814-(benzyloxy)-1-(5-(ethoxymethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-oneYield 73%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-(ethoxymethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (120 mg, 0.20 mmol) in EtOH (2 mL) was added 1 N HCl in Et2O (1 mL). The reaction was stirred at 60° C. until complete. The solvent was concentrated and the residue was purified by preparative HPLC (Phenomenex Luna C18 (2), 250×50 mm, 15 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) to give 4-(benzyloxy)-1-(5-(ethoxymethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one as a white solid (54 mg, 73%). The free base was converted to the HCl salt to give the title compound (35 mg, 65%) as a white powder: mp 148-149° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.12 (s, 2H), 7.66 (d, J=2.0 Hz, 1H), 7.59-7.56 (m, 2H), 7.49-7.37 (m, 5H), 7.08-7.05 (m, 1H), 6.14-6.12 (m, 1H), 5.99 (d, J=2.5 Hz, 1H), 5.57 (s, 2H), 5.17 (s, 2H), 4.38 (m, 2H), 3.55 (m, 2H), 3.45-3.40 (m, 2H), 3.13 (m, 2H), 1.08-1.05 (m, 3H); ESI MS m/z 430 [M+H]+; HPLC (Method A)>99% (AUC), tR=12.8 min.

Workup

  1. concentrationThe solvent was concentrated
  2. customthe residue was purified by preparative HPLC (Phenomenex Luna C18 (2), 250×50 mm, 15 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA)

Sources & evidence

ORD record
ord-1df615b0d2964a0e93ac9bbccc36fafe
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

Loading…