1,4-Dioxane hydrochloride → N-(4-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}phenyl)-N-methylacetamide trihydrochloride

HRID 1047072Notes

Reaction equation

HRID 1047072 reaction equation
[C:1]([N:4]([CH3:47])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[NH:17][C:16]4[N:24]=[CH:25][CH:26]=[CH:27][C:15]=4[N:14]3[C:28]=2[C:29]2[CH:34]=[CH:33][C:32]([C:35]3([NH:39]C(=O)OC(C)(C)C)[CH2:38][CH2:37][CH2:36]3)=[CH:31][CH:30]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[ClH:48].O1CCOCC1>CO>[ClH:48].[ClH:48].[ClH:48].[NH2:39][C:35]1([C:32]2[CH:33]=[CH:34][C:29]([C:28]3[N:14]4[C:15]5[CH:27]=[CH:26][CH:25]=[N:24][C:16]=5[NH:17][C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=5[C:13]4=[N:12][C:11]=3[C:8]3[CH:7]=[CH:6][C:5]([N:4]([CH3:47])[C:1](=[O:3])[CH3:2])=[CH:10][CH:9]=3)=[CH:30][CH:31]=2)[CH2:38][CH2:37][CH2:36]1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 69087686tert-Butyl {1-[4-(2-{4-[acetyl(methyl)amino]phenyl}-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 67503809N-(4-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}phenyl)-N-methylacetamide trihydrochlorideYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl {1-[4-(2-{4-[acetyl(methyl)amino]phenyl}-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (30 mg, 0.048 mmol) in MeOH (0.5 mL) was added 4N HCl-dioxane (2 mL) and stirred at room temperature for 20.5 hours. The mixture was concentrated to afford the desired product (28 mg, 93%) as a yellow solid. 1HNMR (DMSO-d6) 400 MHz δ: 8.68 (br s, 2H), 8.62 (s, 1H), 8.10 (dd, J=4.9 Hz and 1.4 Hz, 1H), 7.96 (dd, J=7.7 Hz and 1.4 Hz, 1H), 7.56 (d, J=8.6 Hz, 3H), 7.37 (d, J=8.6 Hz, 2H), 7.31-7.26 (m, 2H), 7.13 (t, J=8.6 Hz, 1H), 6.88 (dd, J=8.0 Hz and 1.1 Hz, 1H), 6.73 (dd, J=8.0 Hz and 4.6 Hz, 1H), 3.73-3.65 (m, 1H), 3.51-3.45 (m, 1H), 3.17-3.13 (m, 2H), 2.59-2.47 (m, 3H), 2.23-2.15 (m, 2H), 1.88-1.75 (m, 3H). LCMS: 527 [M+H].

Workup

  1. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-9bc80bfdd03f4a84b2d4bbba0ae9214f
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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