Carbon Dioxide → HCID 68512093, compound

HRID 2241191Notes

Reaction equation

HRID 2241191 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([OH:16])=O)[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.C1(C(O)=O)(C(O)=O)CC1.FC1C=CC([NH2:31])=CC=1.C(Cl)(=O)C(Cl)=O.C(=O)=O.[CH3:43][O:44][C:45]1[CH:70]=[CH:69][C:48]([CH2:49][N:50]2[C:54]3=[N:55][CH:56]=[CH:57][C:58]([O:59][C:60]4[CH:65]=[CH:64][C:63](N)=[CH:62][C:61]=4[F:67])=[C:53]3[C:52]([I:68])=[N:51]2)=[CH:47][CH:46]=1>C1COCC1.CO.C(Cl)Cl.C([O-])(O)=O.[Na+].O.CN(C=O)C>[CH3:43][O:44][C:45]1[CH:46]=[CH:47][C:48]([CH2:49][N:50]2[C:54]3=[N:55][CH:56]=[CH:57][C:58]([O:59][C:60]4[CH:65]=[CH:64][C:63]([N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[C:9]([C:11]5([C:14]([NH2:31])=[O:16])[CH2:12][CH2:13]5)=[O:10])=[CH:62][C:61]=4[F:67])=[C:53]3[C:52]([I:68])=[N:51]2)=[CH:69][CH:70]=1

Participants

12

Reactant 6

HCID 280Carbon DioxideHCID 97314-FluoroanilineHCID 65578Oxalyl chlorideHCID 690171,1-Cyclopropanedicarboxylic acidHCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 68512093HCID 68512093, compound

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a stirred solution of 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (0.341 g, 1.53 mmol; prepared from cyclopropane-1,1-dicarboxylic acid and 4-fluoroaniline using the methods of WO 2005/030140 and by Shih and Rankin, Synth. Comm., 1996, 26(4), 833-836), catalytic DMF (5 microliters), and THF (5 mL), was added oxalyl dichloride (0.194 g, 1.53 mmol) at room temperature under N2. The reaction was stirred for 30 minutes at room temperature as CO2 evolved. Then 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.500 g, 1.02 mmol) was added as a solution in THF (2 mL). After stirring for 1 hour at room temperature, the reaction mixture was diluted with 5% MeOH/DCM (100 mL), saturated aqueous NaHCO3 (25 mL), and water (125 mL). The cloudy phases were filtered through celite. The phases were separated, and the organic phase washed with 1N NaOH (50 mL) and then brine (50 mL). The organic phases were dried (Na2SO4), filtered, and concentrated in vacuo. The resulting residue was triturated with diethyl ether (50 mL) and filtered. The solid was discarded. The filtrate was concentrated, and the residue purified by preparative TLC, eluting with 10% MeOH/DCM. The product was used in the next step without further purification. Yield: 25 mg, 2.5%. LRMS (APCI+): m/z 696 (M+1) detected.

Workup

  1. filtrationThe cloudy phases were filtered through celite
  2. customThe phases were separated
  3. washthe organic phase washed with 1N NaOH (50 mL)
  4. dry with materialThe organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was triturated with diethyl ether (50 mL)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. customthe residue purified by preparative TLC
  11. washeluting with 10% MeOH/DCM
  12. customThe product was used in the next step without further purification

Sources & evidence

ORD record
ord-635ade91c4b34907b894784f365d88d1
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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