Cesium carbonate → 7-(3-(trifluoromethyl)pyridin-2-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1,8-naphthyridin-4-amine

HRID 1724880ノート

反応式

HRID 1724880 の反応式
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=1)=[N:7]2.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:19][C:18]([F:21])([F:20])[C:17]1[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:31])([F:30])[F:32])=[CH:25][N:24]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)=[N:13][CH:14]=[CH:15][CH:16]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 462035425-Chloro-2-(3-(trifluoromethyl)pyridin-2-yl)-[1,8]naphthyridine

生成物 1

HCID 462038647-(3-(trifluoromethyl)pyridin-2-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1,8-naphthyridin-4-amine

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

Heat a mixture of 5-chloro-2-(3-(trifluoromethyl)pyridin-2-yl)-[1,8]naphthyridine (62 mg, 0.2 mmol), 2-amino-5-trifluoromethylpyridine (32.4 mg, 0.2 mmol), xantphos (11.6 mg, 0.02 mmol), Pd2(dba)3 (18.3 mg, 0.02 mmol) and Cs2CO3 (130 mg, 0.4 mmol) in dioxane (2.0 mL) at 100° C. for 20 hours. Cool the mixture, concentrate under vacuum, dilute with EtOAc/water (5.0 mL each), filter through celite, wash celite with EtOAc (2×5 mL) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify by preparative TLC using EtOAc as eluent to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.15 (s, 1H), 9.1 (d, 1H, J=2.2 Hz), 9.0 (d, 1H, J=1.1 Hz), 8.95 (d, 1H, J=1.2 Hz), 8.68 (s, 1H), 8.50 (d, 1H, J=1.3 Hz), 8.43 (d, 1H, J=2.0 Hz), 8.12 (dd, 1H), 8.0(d, 1H, J=2.2 Hz), 7.81 (m, 1H), 7.49 (d, 1H, J=2.2 Hz). MS=436.08 (M+H).

後処理

  1. temperatureHeat
  2. temperatureCool the mixture
  3. concentrationconcentrate under vacuum
  4. additiondilute with EtOAc/water (5.0 mL each)
  5. filtrationfilter through celite
  6. washwash celite with EtOAc (2×5 mL)
  7. customdry
  8. filtrationFilter the dried
  9. extractionextract
  10. concentrationconcentrate under vacuum
  11. customto afford crude product
  12. customPurify by preparative TLC

出典と根拠

ORDレコード
ord-6e717f08228b48eba707164519683d7e
出典データセット
uspto-grants-2009_02
特許番号
US07488740B2

反応ノート

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