N,N-Dimethyl-1,3-propanediamine → HCID 131727218, compound

HRID 2237287Notes

Reaction equation

HRID 2237287 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])=[CH:11][C:10]=2[F:26])[CH:5]=[CH:4][N:3]=1.[CH3:27][N:28]([CH3:33])[CH2:29][CH2:30][CH2:31][NH2:32].C([O-])([O-])=O.[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>Cl[Cu].CN1C(=O)CCC1>[ClH:1].[CH3:27][N:28]([CH3:33])[CH2:29][CH2:30][CH2:31][NH:32][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])=[CH:11][C:10]=2[F:26])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 59852933HCID 59852933, compound

Product 1

HCID 131727218HCID 131727218, compoundYield 7.7%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-(4-(2-chloropyridin-4-yloxy)-3-fluorophenyl)-2,6-difluorobenzamide (70 mg, 0.19 mmol), 3-(dimethylamino)propylamine (44 mL, 0.35 mmol), Cs2CO3 (85 mg, 0.26 mmol) and CuCl (17 mg, 0.17 mmol) in a screw capped vial was purged with N2. NMP and 2,2,6,6,-tetramethyl-3,5-heptanedione (31 mg, 0.17 mmol) were added to the mixture which was then heated at 120° C. for 4 h. The mixture was cooled, partitioned between EtOAc and saturated aq. NaHCO3 solution and the EtOAc phase was separated, dried (MgSO4) and concentrated in vacuo to give the crude product. Purification of the residue by preparative HPLC (Column C) and conversion to the hydrochloride salt was carried out in a similar manner as Step D of Example 33 to give the title compound (7 mg, 7%) as an off-white solid. MS(ESI+): m/z 517.37 (M+H)+.

Workup

  1. customcapped vial
  2. customwas purged with N2
  3. temperatureThe mixture was cooled
  4. custompartitioned between EtOAc and saturated aq. NaHCO3 solution
  5. customthe EtOAc phase was separated
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customPurification of the residue by preparative HPLC (Column C) and conversion to the hydrochloride salt

Sources & evidence

ORD record
ord-0ff5b9ccc06a49799ed3e4287b937c26
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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