Triethylamine → HCID 59781131, compound

HRID 606144Notes

Reaction equation

HRID 606144 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[OH:8].Cl[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([NH2:33])[CH:28]=1.C(N(CC)CC)C>CN1C(=O)CCC1.CN(C1C=CN=CC=1)C>[NH2:33][C:29]1[CH:28]=[C:27]([O:8][C:7]2[CH:6]=[CH:5][C:4]([NH:9][C:10]3[N:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:11]=3[C:12]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:13])=[CH:3][C:2]=2[F:1])[CH:32]=[CH:31][N:30]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 5818662-Amino-4-chloropyridine2×HCID 59781134HCID 59781134, compound

Product 1

HCID 59781131HCID 59781131, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

365 mg of a mixture of 2-(3-fluoro-4-hydroxyphenylamino)-5-methyl-N-phenylnicotinamide and the des-methyl analog and 4-chloropyridin-2-amine (264 mg, 2054 μmol) were dissolved in NMP (5.0 ml) and triethylamine (0.75 ml, 5381 μmol) was added. The flask was fitted with a reflux condenser, placed in a preheated oil bath (185° C.-190° C.), and stirred under argon. After about 22 hours, more 4-chloropyridin-2-amine (250 mg, 1.95 mmol), DMAP (171 mg, 1.40 mmol), triethylamine (0.30 ml, 4.1 mmol), and NMP (1 ml) were added, and stirring was continued at 190 C for another day. The reaction was then cooled to room temperature and quenched with water (20 ml). The water was decanted, and the residual solid was collected with DCM and MeOH, concentrated, and purified on silica gel (50:1→25:1 DCM/MeOH→15:1 DCM/2 N ammonia in MeOH) to afford the desired 2-(4-(2-aminopyridine-4-yloxy)-3-fluorophenylamino)-5-methyl-N-phenylnicotinamide along with the des-methyl analog. This mixture was taken to the last step.

Workup

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. stirringstirring
  4. waitwas continued at 190 C for another day
  5. customquenched with water (20 ml)
  6. customThe water was decanted
  7. customthe residual solid was collected with DCM and MeOH
  8. concentrationconcentrated
  9. custompurified on silica gel (50:1→25:1 DCM/MeOH→15:1 DCM/2 N ammonia in MeOH)

Sources & evidence

ORD record
ord-4528df56c592450b8a946853f6d3dadd
Source dataset
uspto-grants-2011_03
Patent number
US07915287B2

Reaction notes

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