1,4-Dioxane hydrochloride → methyl 5-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}pyridine-2-carboxylate tetrahydrochloride

HRID 1047054Notes

Reaction equation

HRID 1047054 reaction equation
C(OC([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]4[C:24]5[CH:36]=[CH:35][CH:34]=[N:33][C:25]=5[NH:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=5[C:22]4=[N:21][C:20]=3[C:37]3[CH:38]=[CH:39][C:40]([C:43]([O:45][CH3:46])=[O:44])=[N:41][CH:42]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=O)(C)(C)C.[ClH:47].O1CCOCC1>CO>[ClH:47].[ClH:47].[ClH:47].[ClH:47].[NH2:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]4[C:24]5[CH:36]=[CH:35][CH:34]=[N:33][C:25]=5[NH:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=5[C:22]4=[N:21][C:20]=3[C:37]3[CH:38]=[CH:39][C:40]([C:43]([O:45][CH3:46])=[O:44])=[N:41][CH:42]=3)=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH2:12]1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 67503711Methyl 5-[3-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl]pyridine-2-carboxylate

Product 1

HCID 67503687methyl 5-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}pyridine-2-carboxylate tetrahydrochlorideYield 88%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 5-[3-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl]pyridine-2-carboxylate (52 mg, 0.085 mmol) in MeOH (0.5 mL) was added 4N HCl-dioxane (2 mL) and stirred at r.t for 23 hours. The mixture was concentrated to afford the desired product (49 mg, 88%) as an orange solid. 1HNMR (DMSO-d6) 400 MHz δ: 8.70-8.68 (m, 1H), 8.65 (br s, 1H), 8.63 (s, 1H), 8.56 (d, J=2.3 Hz, 1H), 8.16 (dd, J=8.0 Hz and 2.3 Hz, 1H), 8.10 (dd, J=4.6 Hz and 1.7 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.97 (dd, J=8.0 Hz and 1.7 Hz, 1H), 7.57 (d, J=8.6 Hz, 2H), 7.39-7.35 (m, 3H), 7.29 (d, J=7.4 Hz, 1H), 7.12 (td, J=8.0 Hz and 1.1 Hz, 1H), 6.91 (dd, J=8.6 Hz and 1.1 Hz, 1H), 6.73 (dd, J=8.0 Hz and 4.6 Hz, 1H), 3.84 (s, 3H), 2.60-2.56 (m, 2H), 2.55-2.50 (m, 2H), 2.21-2.13 (m, 1H), 1.86-1.77 (m, 1H). LCMS: 515 [M+H].

Workup

  1. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-d3f8b65c708f4c8d940a8ed944e12b0d
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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