Sodium Bicarbonate → HCID 86624986, compound

HRID 599521Notes

Reaction equation

HRID 599521 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:34]1[N:41]=[CH:40][C:39]([CH2:42][N:43]2[CH2:48][CH2:47][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:45][CH2:44]2)=[CH:38][C:35]=1[C:36]#[N:37].C(=O)([O-])O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[C:36]([C:35]1[C:34]([C:20]2[CH:19]=[CH:18][C:17]([C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:32])=[CH:22][CH:21]=2)=[N:41][CH:40]=[C:39]([CH2:42][N:43]2[CH2:44][CH2:45][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:47][CH2:48]2)[CH:38]=1)#[N:37]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 59830883N-(2-t-Butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 59848790HCID 59848790, compound

Product 1

HCID 86624986HCID 86624986, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

1,1′-Bis(diphenylphosphino)ferrocenedichloropalladium (II) chloride (58 mg, 0.072 mmol) was added to a mixture of N-(2-t-butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (626 mg, 1.43 mmol prepared as described in International Patent Publication Number WO03/087057, Method 13, page 60), 2-chloro-5-[(4-isopropylpiperazin-1-yl)methyl]nicotinonitrile (398 mg, 1.43 mmol; see Method 20), saturated aqueous sodium hydrogen carbonate solution (5 ml) and 1,2-dimethoxyethane (10 ml). The mixture was heated at 80° C. for 1 hour then allowed to cool to room temperature and partitioned between dichloromethane (75 ml) and water (50 ml). The aqueous layer was extracted with further dichloromethane (2×75 ml). The combined organics were dried over magnesium sulfate, filtered and then evaporated to dryness. The residue was purified by flash chromatography on silica, eluting with methanol (5-10%) in dichloromethane to afford the title compound as a yellow gum which crystallised on trituration with diethyl ether, (652 mg, 82%).

Workup

  1. temperatureto cool to room temperature
  2. custompartitioned between dichloromethane (75 ml) and water (50 ml)
  3. extractionThe aqueous layer was extracted with further dichloromethane (2×75 ml)
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography on silica
  8. washeluting with methanol (5-10%) in dichloromethane

Sources & evidence

ORD record
ord-4cd109ca320c45ceb3a072ef146053f8
Source dataset
uspto-grants-2011_03
Patent number
US07897778B2

Reaction notes

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