Dimethylformamide → MK-3328

HRID 40725Notes

Reaction equation

HRID 40725 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=[C:5]2[CH:4]=[CH:3]1.F[C:15]1[C:20]([NH2:21])=[CH:19][CH:18]=[C:17]([F:22])[N:16]=1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.N1C=CC=CC=1>[F:22][C:17]1[N:16]=[C:15]2[O:13][C:11]([C:9]3[CH:10]=[C:5]4[CH:4]=[CH:3][N:2]([CH3:1])[C:6]4=[N:7][CH:8]=3)=[N:21][C:20]2=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 450800062,6-Difluoropyridin-3-amineHCID 497590021-Methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid

Product 1

HCID 44555286MK-3328Yield 13%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a suspension of 1-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (68 mg, 0.38 mmol) in CH2Cl2 (2 mL) was added 1-chloro-N,N-2-trimethylpropenylamine (50 μL, 0.38 mmol). Following formation of the resulting acid chloride, the reaction mixture was concentrated affording a residue that was dissolved in pyridine (2 mL) before 2,6-difluoro-pyridin-3-ylamine (50 mg, 0.38 mmol) was added in one portion. After an additional 30 minutes the reaction mixture was concentrated to dryness affording a residue, to which was added DMF (2 mL) and K2CO3 (53 mg, 0.38 mmol). The resulting mixture was heated by microwave to 150° C. for 10 min, after which the resulting mixture was filtered and concentrated. The resulting residue was purified by reverse phase chromatography affording 5-fluoro-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-oxazolo[5,4-b]pyridine (13.1 mg, 0.049 mmol, 13% yield). ES MS (M+H+)=269; 1H NMR δ (ppm)(DMSO-d6): 9.07 (1H, d, J=2.12 Hz), 8.75 (1H, d, J=2.13 Hz), 8.42 (1H, t, J=7.74 Hz), 7.70 (1H, d, J=3.52 Hz), 7.29 (1H, d, J=8.41 Hz), 6.69 (1H, d, J=3.52 Hz), 3.89 (3H, s); HRMS m/z 269.0831 (C14H9FN4O+H+ requires 269.0833).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customaffording a residue that
  3. additionwas added in one portion
  4. concentrationAfter an additional 30 minutes the reaction mixture was concentrated to dryness
  5. customaffording a residue
  6. filtrationafter which the resulting mixture was filtered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-652c06358546455bb8c66d58e95227c7
Source dataset
uspto-grants-2013_09
Patent number
US08530483B2

Reaction notes

Loading…