Dimethylformamide → HCID 11177047, compound

HRID 734745Notes

Reaction equation

HRID 734745 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][C:13](=[O:15])[NH:12][C:11]([CH3:16])=[C:10]1[C:17]([OH:19])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[F:31][C:32]1[CH:40]=[C:39]2[C:35]([CH:36]=[N:37][NH:38]2)=[CH:34][C:33]=1[NH2:41]>C(Cl)Cl.N1C=CC=CC=1.CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][C:13](=[O:15])[NH:12][C:11]([CH3:16])=[C:10]1[C:17]([NH:41][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][C:32]=1[F:31])[NH:38][N:37]=[CH:36]2)=[O:19]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 220489194-(2,4-Difluorophenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylic acidHCID 450905046-fluoro-1H-indazol-5-amine

Product 1

HCID 11177047HCID 11177047, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product from Step 2 (80 mg, 0.30 mmol) was suspended in CH2Cl2 (3 mL) under Argon. DMF (20 μL) was added, followed by oxalyl chloride (27 μL, 0.30 mmol). This mixture was stirred at room temperature for 30 min, and the resultant yellow solution was added to a solution of 6-fluoro-1H-indazol-5-amine (50 mg, 0.33 mmol) in pyridine (3 mL) at −15° C. under Ar. After the reaction was stirred at −15° C. for 15 min, the reaction mixture was allowed to warm to room temperature over 1 h. The mixture was then poured into EtOAc (50 mL), washed sequentially with aq. NH4Cl (20 mL), NaOH (10 mL, 2.5 N), HCl (10 mL, 1.0 N) and brine. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was triturated with 10% EtOAc/10% ether/80% hexanes to afford the title compound (78 mg, 65%). MS (ES+) m/e 401 [M+H]+.

Workup

  1. stirringAfter the reaction was stirred at −15° C. for 15 min
  2. temperatureto warm to room temperature over 1 h
  3. washwashed sequentially with aq. NH4Cl (20 mL), NaOH (10 mL, 2.5 N), HCl (10 mL, 1.0 N) and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was triturated with 10% EtOAc/10% ether/80% hexanes

Sources & evidence

ORD record
ord-582763da9b2e44a2bdd7afd3543e341f
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

Loading…