Phenyl isocyanate → tert-butyl {1-[4-(2-{3-[(anilinocarbonyl)amino]phenyl}-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

HRID 1047090Notes

Reaction equation

HRID 1047090 reaction equation
CCN(CC)CC.[C:8]1([N:14]=[C:15]=[O:16])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[NH2:17][C:18]1[CH:19]=[C:20]([C:24]2[N:25]=[C:26]3[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[NH:30][C:29]4[N:37]=[CH:38][CH:39]=[CH:40][C:28]=4[N:27]3[C:41]=2[C:42]2[CH:47]=[CH:46][C:45]([C:48]3([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:51][CH2:50][CH2:49]3)=[CH:44][CH:43]=2)[CH:21]=[CH:22][CH:23]=1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[NH:14]([C:15]([NH:17][C:18]1[CH:19]=[C:20]([C:24]2[N:25]=[C:26]3[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[NH:30][C:29]4[N:37]=[CH:38][CH:39]=[CH:40][C:28]=4[N:27]3[C:41]=2[C:42]2[CH:47]=[CH:46][C:45]([C:48]3([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:57])([CH3:56])[CH3:58])[CH2:49][CH2:50][CH2:51]3)=[CH:44][CH:43]=2)[CH:21]=[CH:22][CH:23]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 69087660tert-Butyl (1-{4-[2-(3-aminophenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate

Product 1

HCID 69087690tert-butyl {1-[4-(2-{3-[(anilinocarbonyl)amino]phenyl}-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamateYield 73.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Et3N (29.3 μL, 0.260 mmol) and phenyl isocyanate (8.0 μL, 0.0771 mmol) were added to a solution of tert-butyl (1-{4-[2-(3-aminophenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate (40.0 mg, 0.0701 mmol) in DCM (1 mL) at 0° C., and stirred at room temperature. After reaction was completed, the mixture was diluted with sat. NaHCO3 and extracted with CHCl3 (3×). The combined organic layers were dried over anhydrous Na2SO4, and concentrated. The residue was purified by PTLC (CHCl3/MeOH=9:1) to afford desired product (35.4 mg, 69.3%) as white solid. 1HNMR (DMSO-d6) 400 MHz δ: 8.15 (dd, J=7.8, 1.4 Hz, 1H), 8.05 (dd, J=4.6, 1.8 Hz, 1H), 7.90-6.59 (m, 20H), 6.30 (s, 1H), 6.18-5.38 (m, 1H), 2.67-2.54 (m, 2H), 2.52-2.39 (m, 2H), 2.25-2.10 (m, 1H), 2.06-1.86 (m, 1H), 1.37 (s, 9H).

Workup

  1. customAfter reaction
  2. extractionextracted with CHCl3 (3×)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by PTLC (CHCl3/MeOH=9:1)

Sources & evidence

ORD record
ord-6ebee7ca033d4faf9ae80ff52b077706
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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