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

HRID 1046997Notes

Reaction equation

HRID 1046997 reaction equation
[N:1]1[CH:2]=[C:3]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[NH:7][C:6]1[N:15]=[CH:16][CH:17]=[CH:18][C:5]2=1.C1C=C[NH+]=CC=1.[Br:43][Br-]Br.C(OCC)(=O)C.O>C1COCC1>[Br:43][C:2]1[N:1]=[C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[NH:7][C:6]3[N:15]=[CH:16][CH:17]=[CH:18][C:5]=3[N:4]2[C:3]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:26][CH2:27][CH2:28]2)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 962WaterHCID 8857Ethyl AcetateHCID 69087639tert-butyl {1-[4-(9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 136331865tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamateYield 59.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

tert-Butyl {1-[4-(9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (9.8 g, 20.4 mmol) was dissolved in THF (350 mL). A solution of pyridinium bromide perbromide (6.5 g, 20.4 mmol) in THF (50 mL) was added to the mixture at −78° C. After three hours stirring at r.t., pyridinium bromide perbromide (2.6 g, 8.2 mmol) in THF was added to the mixture and the mixture was stirred at rt overnight. The mixture was poured into ethyl acetate (1.5 L) and mixed with water and separated. The combined organic phase was washed with saturated sodium bicarbonate solution in water, then dried with anhydrous sodium sulfate and evaporated. The residue was purified with silica gel column chromatography (dichloromethane/ethyl acetate, 20:1) to give the titled compound as a white solid (6.8 g, 59%). 1HNMR (CDCl3) 400 MHz δ: 8.04 (d, J=8.0 Hz, 2H), 7.40 (d, J=7.4 Hz, 2H), 7.31 (t, J=7.4 Hz, 1H), 7.23 (d, J=6.9 Hz, 2H), 7.12 (t, J=7.7 Hz, 1H), 6.94 (d, J=8.0 Hz, 1H), 6.88-6.80 (m, 1H), 6.66-6.62 (m, 1H), 6.29 (s, 1H), 5.10 (s, 1H), 2.58-2.37 (m, 4H), 2.18-2.08 (m, 1H), 1.94-1.84 (m, 1H), 1.39 (br s, 9H); LC/MS [M+H]: 558

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. customseparated
  3. washThe combined organic phase was washed with saturated sodium bicarbonate solution in water
  4. dry with materialdried with anhydrous sodium sulfate
  5. customevaporated
  6. customThe residue was purified with silica gel column chromatography (dichloromethane/ethyl acetate, 20:1)

Sources & evidence

ORD record
ord-13e1f53446f64865b19f1d1dc3360845
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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