1,4-Dioxane hydrochloride → HCID 178507118, compound

HRID 1047061Notes

Reaction equation

HRID 1047061 reaction equation
C[O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[NH:15][C:14]4[N:22]=[CH:23][CH:24]=[CH:25][C:13]=4[N:12]3[C:26]=2[C:27]2[CH:32]=[CH:31][C:30]([C:33]3([NH:37]C(=O)OC(C)(C)C)[CH2:36][CH2:35][CH2:34]3)=[CH:29][CH:28]=2)=[CH:5][N:4]=1.Cl.O1CCOCC1>CO>[NH2:37][C:33]1([C:30]2[CH:31]=[CH:32][C:27]([C:26]3[N:12]4[C:13]5[CH:25]=[CH:24][CH:23]=[N:22][C:14]=5[NH:15][C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=5[C:11]4=[N:10][C:9]=3[C:6]3[CH:7]=[N:8][C:3]([OH:2])=[N:4][CH:5]=3)=[CH:28][CH:29]=2)[CH2:36][CH2:35][CH2:34]1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 69087665tert-Butyl (1-{4-[2-(2-methoxypyrimidin-5-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate

Product 1

HCID 178507118HCID 178507118, compoundYield 19.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl (1-{4-[2-(2-methoxypyrimidin-5-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate (45 mg, 0.077 mmol) in MeOH (0.5 mL) was added 4N HCl-dioxane (2 mL) and stirred at r.t for 19 hours. The mixture was concentrated, then sat.NaHCO3 aq. was added. The mixture was extracted with CH2Cl2+MeOH (×3), dried over Na2SO4, then filtrated through Celite pad. The filtrate was concentrated and the residue was purified by preparative thin-layer chromatography (CH2Cl2/MeOH=4:1) to afford the desired product (7 mg, 18%) as a yellow solid. 1HNMR (DMSO-d6) 400 MHz δ: 8.58 (s, 1H), 8.23 (br s, 2H), 8.09 (dd, J=4.6 Hz and 1.7 Hz, 1H), 7.92 (dd, J=4.6 Hz and 1.1 Hz, 1H), 7.51 (d, J=8.6 Hz, 2H), 7.34 (td, J=8.6 Hz and 1.7 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.23 (d, J=7.4 Hz, 2H), 7.10 (td, J=7.4 Hz and 1.1 Hz, 1H), 6.87 (dd, J=8.0 Hz and 1.7 Hz, 1H), 6.76 (dd, J=8.0 Hz and 4.6 Hz, 1H), 2.44-2.39 (m, 2H), 2.20-2.15 (m2H), 2.09-2.00 (m, 1H), 1.74-1.67 (m, 1H). LCMS: 474 [M+H].

Workup

  1. concentrationThe mixture was concentrated
  2. additionNaHCO3 aq. was added
  3. extractionThe mixture was extracted with CH2Cl2+MeOH (×3)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltrated through Celite pad
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by preparative thin-layer chromatography (CH2Cl2/MeOH=4:1)

Sources & evidence

ORD record
ord-bf20db57126d440298c657d0e3401e8a
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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