Diisopropylethylamine → (1S,2S)-N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamide

HRID 468900Notes

Reaction equation

HRID 468900 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH2:12])[N:8]=[CH:9]2)=[CH:4][N:3]=1.[F:13][C@H:14]1[CH2:16][C@H:15]1[C:17](O)=[O:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:17]([C@@H:15]3[CH2:16][C@@H:14]3[F:13])=[O:18])[N:8]=[CH:9]2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9793716cis-2-Fluorocyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866749727-Chloro-2,6-naphthyridin-3-amine

Product 1

HCID 86674973(1S,2S)-N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamideYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 7-chloro-2,6-naphthyridin-3-amine (230 mg, 1.3 mmol), (1S,2S)-2-fluorocyclopropanecarboxylic acid (266 mg, 2.6 mmol), HATU (1.1 g, 2.8 mmol), and N,N-diisopropylethylamine (0.45 mL, 2.6 mmol) in N,N-dimethylformamide (3 mL) was heated at 70° C. for 16 hours. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 12 g, ISCO, 0-60% ethyl acetate in heptane) to afford the title compound as a white solid (150 mg, 44%). 1H NMR (400 MHz, DMSO) δ 11.22 (s, 1H), 9.29 (s, 1H), 9.28 (s, 1H), 8.66 (s, 1H), 8.16 (s, 1H), 5.08-4.85 (m, 1H), 2.29 (m, 1H), 1.71 (m, 1H), 1.22 (m, 1H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 12 g, ISCO, 0-60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-cf41f9d4351848c6abf1d379e90d02d2
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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