Dimethylformamide → (S)-7-fluoro-N-((3-fluoro-4-methoxyphenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-1,6-naphthyridine-2-carboxamide

HRID 1051362Notes

Reaction equation

HRID 1051362 reaction equation
CN(C(ON1N=[N:16][C:11]2[CH:12]=[CH:13][CH:14]=N[C:10]1=2)=[N+](C)C)C.[F:18][P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:34][N:35]([CH:37]=O)C.Cl.[F:40][C:41]1[CH:42]=[C:43]([C@@H:49]([C:51]2[CH:52]=[N:53][N:54]([CH3:56])[CH:55]=2)[NH2:50])[CH:44]=[CH:45][C:46]=1[O:47][CH3:48].CCO[C:60]([CH3:62])=[O:61]>>[F:18][C:34]1[CH:10]=[C:11]2[C:12]([CH:13]=[CH:14][C:62]([C:60]([NH:50][C@@H:49]([C:43]3[CH:44]=[CH:45][C:46]([O:47][CH3:48])=[C:41]([F:40])[CH:42]=3)[C:51]3[CH:52]=[N:53][N:54]([CH3:56])[CH:55]=3)=[O:61])=[N:16]2)=[CH:37][N:35]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86712001(S)-(3-fluoro-4-methoxy-phenyl)-(1-methylpyrazol-4-yl)methanamine hydrochloride

Product 1

HCID 86712000(S)-7-fluoro-N-((3-fluoro-4-methoxyphenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-1,6-naphthyridine-2-carboxamide

Procedure

A mixture of 74 (45 mg, 0.234 mmol), HATU (133.57 mg, 0.351 mmol), and DIPEA (0.123 mL, 0.703 mmol) in DMF (0.546 mL, 7.03 mmol) was stirred at RT for 5 min. To the solution was added in one portion (S)-(3-fluoro-4-methoxy-phenyl)-(1-methylpyrazol-4-yl)methanamine hydrochloride (50c) (76.36 mg, 0.281 mmol) and the reaction mixture was stirred at RT for 1 h. The reaction mixture was diluted with EtOAc (30 mL) and washed with water (20 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue that was purified by SiO2 chromatography eluting a with an EtOAc/heptane gradient (0 to 100% EtOAc) to afford 80 mg (83%) of (S)-7-fluoro-N-((3-fluoro-4-methoxyphenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-1,6-naphthyridine-2-carboxamide (76) as a yellow oil (80 mg, 83%), which was used in the next step without further purification.

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 h
  2. washwashed with water (20 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue that was purified by SiO2 chromatography
  8. washeluting a with an EtOAc/heptane gradient (0 to 100% EtOAc)

Sources & evidence

ORD record
ord-70f998477b8448cd987e2a72621ccd25
Source dataset
uspto-grants-2016_07
Patent number
US09388171B2

Reaction notes

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