Hydrochloric Acid → HCID 22240472, compound

HRID 1931155Notes

Reaction equation

HRID 1931155 reaction equation
[NH2:1][C:2]([C:4]1[CH:8]=[C:7]([C:9]([OH:11])=O)[N:6]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([C:19]#[N:20])[CH:13]=2)[N:5]=1)=[O:3].[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N=[C:31]=[N:32][CH:33]([CH3:35])[CH3:34])(C)C.Cl>CN(C=O)C>[C:19]([C:14]1[CH:13]=[C:12]([N:6]2[C:7]([C:9]([N:21]3[C:22]4[C:24](=[CH:23][CH:35]=[C:33]([N:32]5[CH2:31][CH2:9][CH2:7][CH2:8][CH2:4][C:2]5=[O:3])[CH:34]=4)[CH2:25][CH2:26]3)=[O:11])=[CH:8][C:4]([C:2]([NH2:1])=[O:3])=[N:5]2)[CH:17]=[CH:16][C:15]=1[F:18])#[N:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 12734DiisopropylcarbodiimideHCID 21936836HCID 21936836, compound

Product 1

HCID 22240472HCID 22240472, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part D. To the product from Part C (90 mg, 0.39 mmol), was added 3-(aminocarbonyl)-1-(3-cyano-4-fluorophenyl)-1H-pyrazole-5-carboxylic acid (89 mg, 0.33 mmol), 3.0 mL of pyridine and 1.0 mL of DMF. 1,3-Diisopropylcarbodiimide (0.056 mL, 0.36 mmol) was added, and the resulting solution was stirred for 14 h. The red mixture was poured into 1N aqueous HCl (70 mL) and washed with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, and filtered. Concentration of the filtrate and purification of the resulting residue by preparative LC/MS (C18 reverse phase, eluted with 0.05% TFA in CH3CN/H2O) gave 1-(3-cyano-4-fluorophenyl)-5-{[6-(2-oxo-hexahydro-1H-azepin-1-yl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1H-pyrazole-3-carboxamide (67, 29% mg) as a white foam. LC/MS (ESI+): 487.2 (M+H)+.

Workup

  1. washwashed with EtOAc (3×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customConcentration of the filtrate and purification of the resulting residue by preparative LC/MS (C18 reverse phase
  6. washeluted with 0.05% TFA in CH3CN/H2O)

Sources & evidence

ORD record
ord-d49e07952e0d48848dfd959cfe6355d6
Source dataset
uspto-grants-2012_05
Patent number
US08188120B2

Reaction notes

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