Sodium Carbonate → HCID 68067477, compound

HRID 1047005Notes

Reaction equation

HRID 1047005 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:46]=[CH:45][C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][CH:42]=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]=[CH:45][C:44]([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:43][CH:42]=1)([O-:40])=[O:39]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27735554,4,5,5-Tetramethyl-2-(4-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 68067477HCID 68067477, compoundYield 17.6%

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 (250 mg, 0.486 mmol), 4-nitrophenylboronic acid pinacol ester (152 mg, 0.730 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (34.4 mg, 0.0486 mmol) and 2M Na2CO3 aq. (0.485 mL, 0.970 mmol) in DMF (1.00 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). 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) and TLC (EtOAc/hexane=1:1, DCM/EtOAc=1:1) to afford desired product (51.4 mg, 17.6%) as yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.19-8.08 (m, 3H), 8.06-8.01 (m, 1H), 7.80-7.70 (m, 2H), 7.47-7.40 (m, 2H), 7.36-7.30 (m, 1H), 7.22-7.14 (m, 3H), 7.00-6.93 (m, 1H), 6.85-6.78 (m, 1H), 6.65-6.58 (m, 1H), 6.38 (s, 1H), 5.19 (s, 1H), 2.67-2.30 (m, 4H), 2.25-2.09 (m, 1H), 1.98-1.84 (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→1:2) and TLC (EtOAc/hexane=1:1, DCM/EtOAc=1:1)

Sources & evidence

ORD record
ord-8c387024d948416eb89f842844502621
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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