Hydrochloric Acid → HCID 22240512, compound

HRID 890520Notes

Reaction equation

HRID 890520 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:23]4[C:24](=[CH:35][C:33]([N:32]5[CH2:31][CH2:9][CH2:7][CH2:8][CH2:4][C:2]5=[O:3])=[CH:34][CH:22]=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 22240512HCID 22240512, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part B. To the product from Part A (95 mg, 0.41 mmol), was added 3-(aminocarbonyl)-1-(3-cyano-4-fluorophenyl)-1H-pyrazole-5-carboxylic acid (94 mg, 0.34 mmol), 3.3 mL of pyridine, and 0.70 mL of DMF. 1,3-Diisopropylcarbodiimide (0.059 mL, 0.38 mmol) was added, and the resulting solution was stirred for 1 h. The red mixture was then 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 radial chromatography (1–5% MeOH in CH2Cl2) gave 1-(3-cyano-4-fluorophenyl)-5-{[5-(2-oxohexahydro-1H-azepin-1-yl)-2,3-dihydro-1H-indol-yl]carbonyl}-1H-pyrazole-3-carboxamide (98 mg, 49%) as a brown residue. LC/MS (ESI+): 487.1 (M+H)+. 1H NMR (CD3OD) δ 8.08 (br m, 1H), 7.97 (br d, 1H), 7.87 (br s, 1H), 7.43 (br t, 1H), 7.28 (s, 1H), 7.12 (br s, 1H), 7.00 (br d, 1H), 4.24 (br m, 2H), 3.73 (br s, 2H), 3.16 (br m, 2H), 2.66 (br s, 2H), 1.79 (br s, 6H).

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 radial chromatography (1–5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-7264d8b931ec4f9da9992f983664f3a7
Source dataset
uspto-grants-2006_02
Patent number
US06995172B2

Reaction notes

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