HCID 69087722, compound → HCID 69087674, compound

HRID 1047050Notes

Reaction equation

HRID 1047050 reaction equation
[C:1]([O:5][C:6](=[O:50])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:22]4[C:23]5[CH:35]=[CH:34][CH:33]=[N:32][C:24]=5[NH:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[C:21]4=[N:20][C:19]=3[C:36]3[CH:41]=[CH:40][C:39]([O:42]CC4C=CC=CC=4)=[CH:38][CH:37]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1.CO.C(Cl)Cl.CO>[OH:42][C:39]1[CH:38]=[CH:37][C:36]([C:19]2[N:20]=[C:21]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[NH:25][C:24]4[N:32]=[CH:33][CH:34]=[CH:35][C:23]=4[N:22]3[C:18]=2[C:15]2[CH:16]=[CH:17][C:12]([C:8]3([NH:7][C:6](=[O:50])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:9][CH2:10][CH2:11]3)=[CH:13][CH:14]=2)=[CH:41][CH:40]=1

Participants

5

Reactant 1

HCID 69087722HCID 69087722, compound

Product 1

HCID 69087674HCID 69087674, compoundYield 97.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
50 °C

Procedure

Atmosphere of tert-butyl[1-(4-{2-[4-(benzyloxy)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl}phenyl)cyclobutyl]carbamate (430 mg, 0.650 mmol) and 10% Pd—C(dry) (43 mg) in THF (7 mL) and MeOH (7 mL) was exchanged to H2 and stirred at 50° C. for 24 hours. The mixture was diluted with CH2Cl2+MeOH and filtrated through Celite pad. The filtrate was concentrated and the reaction was repeated again. Atmosphere of the residue and 10% Pd—C(dry) (43 mg) in THF (21 mL) and MeOH (21 mL) was exchanged to H2 and stirred at 50° C. for 25 hours. The mixture was diluted with CH2Cl2 and filtrated through Celite pad. The filtrate was concentrated and the residue was purified by column chromatography (CH2Cl2/MeOH=5:1) to afford the desired product (362 mg, 97%) as a pale brown solid. 1HNMR (DMSO-d6) 400 MHz δ: 9.42 (s, 1H), 8.51 (s, 1H), 8.04 (d, J=3.4 Hz, 1H), 7.93 (dd, J=7.4, 1.4 Hz, 1H), 7.36-7.26 (m, 5H), 7.14-7.08 (m, 3H), 6.88-6.81 (m, 2H), 6.64 (d, J=8.6 Hz, 2H), 2.42-2.33 (m, 4H), 2.02-1.97 (m, 1H), 1.81-1.74 (m, 1H), 1.34 (br s, 5H), 1.17 (br s, 4H). LCMS: 572 [M+H].

Workup

  1. filtrationfiltrated through Celite pad
  2. concentrationThe filtrate was concentrated
  3. stirringstirred at 50° C. for 25 hours
  4. additionThe mixture was diluted with CH2Cl2
  5. filtrationfiltrated through Celite pad
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by column chromatography (CH2Cl2/MeOH=5:1)

Sources & evidence

ORD record
ord-8cf882b40a1545caac29feb2380df0f5
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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