Dimethylformamide → HCID 25099693, compound

HRID 2381947Notes

Reaction equation

HRID 2381947 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.ClC(C(Cl)=O)=O.[NH2:29][N:30]1[C:38]2[C:33](=[CH:34][C:35]([F:39])=[CH:36][CH:37]=2)[C:32]([CH2:40][C:41]([CH3:44])([OH:43])[CH3:42])=[CH:31]1>C(Cl)Cl.CN(C1C=CN=CC=1)C.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>[F:39][C:35]1[CH:34]=[C:33]2[C:38](=[CH:37][CH:36]=1)[N:30]([NH:29][C:15]([C:11]1[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=1)=[O:17])[CH:31]=[C:32]2[CH2:40][C:41]([OH:43])([CH3:42])[CH3:44]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 68555047HCID 68555047, compound

Product 1

HCID 25099693HCID 25099693, compoundYield 70%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (250 mg, 1.07 mmol) in DCM (10 mL) is cooled to 0° C., treated with DMF (20 μL) and ClCOCOCl (280 μL, 3.21 mmol), and stirred for 20 min. Toluene (10 mL) is added and the mixture is concentrated in vacuo. The residue is dissolved in pyridine (10 mL) and treated with DMAP (5 mg) and 1-(1-amino-5-fluoroindol-3-yl)-2-methyl-propan-2-ol (0.72 mmol). The mixture is stirred at rt for 12 h. The mixture is diluted with saturated aqueous Na2CO3, extracted with EtOAc. The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 20%-60% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(2-hydroxy-2-methyl-propyl)-indol-1-yl]-amide (218 mg, 70%). MS: 437 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 1.14 (s, 6H), 2.77 (s, 2H), 3.29 (s, 3H), 7.03 (m, 1H), 7.37 (s, 1H), 7.35-7.55 (m, 3H), 7.65 (m, 1H), 8.19 (m, 1H), 8.34 (m, 1H), 9.22 (s, 1H).

Workup

  1. concentrationthe mixture is concentrated in vacuo
  2. dissolutionThe residue is dissolved in pyridine (10 mL)
  3. stirringThe mixture is stirred at rt for 12 h
  4. extractionextracted with EtOAc
  5. customThe organic layer is separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with 20%-60% EtOAc in heptane

Sources & evidence

ORD record
ord-c16c7fd827914b309b56215594b40595
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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