Sodium Carbonate → HCID 69087703, compound

HRID 1047080Notes

Reaction equation

HRID 1047080 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]([NH:52][C:53]([CH:55]3[CH2:57][CH2:56]3)=[O:54])=[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>[CH:55]1([C:53]([NH:52][C:49]2[CH:50]=[CH:51][C:46]([C:2]3[N:3]=[C:4]4[C:10]5[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=5[NH:8][C:7]5[N:15]=[CH:16][CH:17]=[CH:18][C:6]=5[N:5]4[C:19]=3[C:20]3[CH:25]=[CH:24][C:23]([C:26]4([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:36])[CH3:34])[CH2:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)=[CH:47][CH:48]=2)=[O:54])[CH2:56][CH2:57]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 67503029HCID 67503029, 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 69087703HCID 69087703, compoundYield 94.3%

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), N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarboxamide (38.6 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) to afford desired product (53.9 mg, 94.3%) as pale yellow solid. 1HNMR (CDCl3) 500 MHz δ: 8.15 (dd, J=7.7, 1.4 Hz, 1H), 8.02-7.97 (m, 1H), 7.70 (br s, 1H), 7.55-7.48 (m, 2H), 7.45-7.38 (m, 2H), 7.36-7.31 (m, 2H), 7.30-7.25 (m, 1H), 7.16-7.10 (m, 3H), 6.95 (d, J=8.0 Hz, 1H), 6.83-6.74 (m, 1H), 6.58 (dd, J=7.7, 4.9 Hz, 1H), 6.55-6.49 (m, 1H), 5.26 (br s, 1H), 2.59-2.24 (m, 4H), 2.19-2.06 (m, 1H), 1.95-1.79 (m, 1H), 1.57-1.19 (m, 10H), 1.09-1.02 (m, 2H), 0.84-0.75 (m, 2H).

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)

Sources & evidence

ORD record
ord-3bced3b6762f4f099e2e2847897f4c1d
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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