Sodium Bicarbonate → HCID 69087722, compound

HRID 1047085Notes

Reaction equation

HRID 1047085 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.C([O-])(O)=O.[Na+].[CH2:43]([O:50][C:51]1[CH:56]=[CH:55][C:54](B(O)O)=[CH:53][CH:52]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C>[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:54]3[CH:55]=[CH:56][C:51]([O:50][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[CH:52][CH:53]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1)([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 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 69087722HCID 69087722, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

To a solution 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 mg, 0.097 mmol) in DMF (1 mL) was added saturated NaHCO3, 4-benzyloxyphenylboronic acid (45 mg, 0.20 mmol) and PdCl2(Me2NPhP(tBu)2)2 (7 mg, 0.0097 mmol). The reaction was degassed for 2 minutes and then heated at 160° C., 1 h (microwave reactor). The reaction mixture was cooled to room temperature, then was diluted with EtOAc (15 mL) and washed with brine. The organic phase was dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (SiO2, 10% to 50% EtOAc in hexane) gave the title compound as a yellow solid (56 mg). 1HNMR (CDCl3) 400 MHz δ: 8.17-8.15 (m, 1H), 8.00-7.99 (m, 1H), 7.51 (d, J=8.6 Hz, 2H), 7.48-7.23 (m, 8H), 7.15-7.13 (m, 3H), 6.94 (d, J=7.4 Hz, 1H), 6.89 (d, J=8.6 Hz, 2H), 6.79 (d, J=7.4 Hz, 1H), 6.59 (dd, J=7.7, 4.9 Hz, 1H), 6.30 (s, 1H), 5.12 (br s, 1H), 5.05 (s, 2H), 2.53-2.51 (m, 4H), 2.15-2.12 (m, 1H), 1.93-1.84 (m, 1H), 1.39 (br s, 9H).

Workup

  1. customThe reaction was degassed for 2 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionwas diluted with EtOAc (15 mL)
  4. washwashed with brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (SiO2, 10% to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-7517bca9c52b47e3b7b8169d6fbbc971
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

Loading…