Sodium Carbonate → HCID 69087699, compound

HRID 1047057Notes

Reaction equation

HRID 1047057 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.[CH3:38][C:39]1[CH:44]=[CH:43][C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][C:40]=1[N+:54]([O-:56])=[O:55].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>[CH3:38][C:39]1[CH:44]=[CH:43][C:42]([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]([CH3:36])([CH3:35])[CH3:34])[CH2:27][CH2:28][CH2:29]3)=[CH:22][CH:21]=2)=[CH:41][C:40]=1[N+:54]([O-:56])=[O:55]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 467387704,4,5,5-Tetramethyl-2-(4-methyl-3-nitrophenyl)-1,3,2-dioxaborolaneHCID 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 69087699HCID 69087699, compoundYield 95.7%

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 (50.0 mg, 0.0835 mmol), 4-methyl-3-nitrophenylboronic acid pinacol ester (33.6 mg, 0.125 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (5.91 mg, 0.00835 mmol) and 2M Na2CO3 aq. (0.0835 mL, 0.170 mmol) in DMF (1.00 mL) was heated at 160° C. under microwave irradiation for 1 hour. After cooling to room temperature, the mixture was diluted with EtOAc and washed with water(×3). The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (EtOAc/hexane=1:4→1:3→1:2) to afford desired product (49.1 mg, 95.7%) as pale yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.21 (s, 1H), 8.16 (dd, J=7.8, 1.4 Hz, 1H), 8.02 (dd, J=4.6, 1.4 Hz, 1H), 7.67 (dd, J=8.2, 1.8 Hz, 1H), 7.42 (d, J=8.2 Hz, 2H), 7.31 (td, J=7.6, 1.5 Hz, 1H), 7.22-7.11 (m, 4H), 7.00-6.93 (m, 1H), 6.85 (d, J=7.8 Hz, 1H), 6.61 (dd, J=7.8, 5.0 Hz, 1H), 6.50 (s, 1H), 5.24 (br s, 1H), 2.67-2.27 (m, 4H), 2.56 (s, 3H), 2.23-2.07 (m, 1H), 1.97-1.85 (m, 1H), 1.39 (br s, 9H).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water(×3)
  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→1:3→1:2)

Sources & evidence

ORD record
ord-50f3ef7d610e4e9daea5c484b04db12d
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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