Sodium Carbonate → tert-Butyl (1-{4-[2-(3-nitrophenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate

HRID 1047045

Reaction equation

HRID 1047045 reaction equation
Cl[C:2]1[N:3]=[C:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:7]3[N:15]=[CH:16][CH:17]=[CH:18][C:6]=3[N:5]2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]2([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.[N+:38]([C:41]1[CH:42]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:44]=[CH:45][CH:46]=1)([O-:40])=[O:39].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[N+:38]([C:41]1[CH:46]=[C:45]([C:2]2[N:3]=[C:4]3[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[NH:8][C:7]4[N:15]=[CH:16][CH:17]=[CH:18][C:6]=4[N:5]3[C:19]=2[C:20]2[CH:25]=[CH:24][C:23]([C:26]3([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:27][CH2:28][CH2:29]3)=[CH:22][CH:21]=2)[CH:44]=[CH:43][CH:42]=1)([O-:40])=[O:39]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 112651643-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nitrobenzeneHCID 136331866tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 69087657tert-Butyl (1-{4-[2-(3-nitrophenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamateYield 96.2%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (291 mg, 0.500 mmol), 3-nitrophenyl boronic acid pinacol ester (187 mg, 0.750 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (35.4 mg, 0.0500 mmol) and 2M Na2CO3 (0.500 mL, 1.00 mmol) in DMF (4.00 mL) was heated at 160° C. under microwave irradiation for 1 hour under nitrogen. After cooling to room temperature, the mixture was diluted with EtOAc and washed with water (×3) and brine. The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (EtOAc/hexane=1:4→1:2) to afford desired product (289 mg, 96.2%) as yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.45 (s, 1H), 8.18 (d, J=7.8 Hz, 1H), 8.07-8.00 (m, 2H), 7.91-7.86 (m, 1H), 7.47-7.36 (m, 3H), 7.34-7.26 (m, 1H), 7.22-7.12 (m, 3H), 6.98 (d, J=7.3 Hz, 1H), 6.90-6.69 (m, 2H), 6.62 (dd, J=7.8, 4.6 Hz, 1H), 5.77-5.09 (m, 1H), 2.65-2.31 (m, 4H), 2.28-2.07 (m, 1H), 1.99-1.82 (m, 1H), 1.39 (br s, 9H).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (×3) and brine
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (EtOAc/hexane=1:4→1:2)

Sources & evidence

ORD record
ord-a04add3299dd4967b555837032633f5c
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Linked notes

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