Sodium Carbonate → HCID 69087689, compound

HRID 1047077Notes

Reaction equation

HRID 1047077 reaction equation
Br[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.CC1(C)C(C)(C)OB([C:46]2[CH:51]=[CH:50][C:49]([N:52]3[CH2:57][CH2:56][CH2:55][CH2:54][C:53]3=[O:58])=[CH:48][CH:47]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)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>[C:33]([O:32][C:31](=[O:37])[NH:30][C:26]1([C:23]2[CH:24]=[CH:25][C:20]([C:19]3[N:5]4[C:6]5[CH:18]=[CH:17][CH:16]=[N:15][C:7]=5[NH:8][C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=5[C:4]4=[N:3][C:2]=3[C:46]3[CH:51]=[CH:50][C:49]([N:52]4[CH2:57][CH2:56][CH2:55][CH2:54][C:53]4=[O:58])=[CH:48][CH:47]=3)=[CH:21][CH:22]=2)[CH2:29][CH2:28][CH2:27]1)([CH3:35])([CH3:34])[CH3:36]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 24774131HCID 24774131, compoundHCID 136331865tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 69087689HCID 69087689, compoundYield 54.6%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (50.0 mg, 0.0895 mmol), 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidin-2-one (40.5 mg, 0.134 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6.34 mg, 0.00895 mmol) and 2 M Na2CO3 (0.0895 mL, 0.179 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 water 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, EtOAc/CHCl3=1:1) to afford desired product (31.9 mg, 54.6%) as a pale yellow solid. 1HNMR (CDCl3) 500 MHz δ: 8.16 (dd, J=7.7, 1.4 Hz, 1H), 8.03-7.97 (m, 1H), 7.61 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 2H), 7.31-7.25 (m, 1H), 7.21-7.10 (m, 5H), 6.95 (d, J=7.4 Hz, 1H), 6.84-6.69 (m, 1H), 6.59 (dd, J=8.0, 4.6 Hz, 1H), 6.51-6.45 (m, 1H), 5.21 (br s, 1H), 3.64-3.57 (m, 2H), 2.61-2.26 (m, 6H), 2.18-2.07 (m, 1H), 1.97-1.80 (m, 5H), 1.40 (br s, 9H).

Workup

  1. temperatureAfter cooling to room temperature
  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, EtOAc/CHCl3=1:1)

Sources & evidence

ORD record
ord-8ce5a473cce5490ba8dc2c4a68df7377
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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