Ethyl bromoacetate → HCID 178452586, compound

HRID 1047089Notes

Reaction equation

HRID 1047089 reaction equation
[NH2:1][C:2]([NH:4][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:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:38][CH2:37][CH2:36]3)=[CH:31][CH:30]=2)=[CH:7][CH:6]=1)=[S:3].Br[CH2:48][C:49](OCC)=[O:50]>CCO.C1COCC1.C(Cl)(Cl)Cl>[O:50]=[C:49]1[CH2:48][S:3][C:2]([NH:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[N:12]=[C:13]4[C:19]5[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=5[NH:17][C:16]5[N:24]=[CH:25][CH:26]=[CH:27][C:15]=5[N:14]4[C:28]=3[C:29]3[CH:34]=[CH:33][C:32]([C:35]4([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:43])([CH3:45])[CH3:44])[CH2:36][CH2:37][CH2:38]4)=[CH:31][CH:30]=3)=[CH:9][CH:10]=2)=[N:1]1

Participants

6

Reactant 2

HCID 7748Ethyl bromoacetateHCID 86664677HCID 86664677, compound

Product 1

HCID 178452586HCID 178452586, compoundYield 91.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl {1-[4-(2-{4-[(aminocarbonothioyl)amino]phenyl}-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (53 mg, 0.083 mmol) in EtOH (2 mL), THF (1 mL) and CHCl3 (1 mL) was added ethyl bromoacetate (0.01 mL, 0.09 mmol). The reaction was heated at 70° C., 1.5 h. The reaction mixture was cooled to room temperature, then concentrated. Purification by column chromatography (SiO2, 50% to 100% EtOAc in hexane) gave the title compound as a yellow solid (51 mg, 91%). 1HNMR (CDCl3) 400 MHz δ: 8.16 (d, J=8.0 Hz, 1H), 8.02-8.01 (m, 1H), 7.62-7.61 (m, 2H), 7.40-7.35 (m, 2H), 7.32-7.29 (m, 1H), 7.20-7.13 (m, 3H), 7.05-7.04 (m, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.80-6.78 (m, 1H), 6.60 (dd, J=8.0, 4.6 Hz, 1H), 6.36 (br s, 1H), 5.18 (br s, 1H), 3.90-3.88 (m, 2H), 2.54-2.52 (m, 4H), 2.16-2.12 (m, 1H), 1.92-1.90 (m, 1H), 1.39 (br s, 9H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customPurification by column chromatography (SiO2, 50% to 100% EtOAc in hexane)

Sources & evidence

ORD record
ord-6f683cb6d40d40d0a2fbd2d11f9507a1
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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