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

HRID 1502417노트

반응식

HRID 1502417 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
70 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-8cb1b9a188a54cab8fb305bb17959767
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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