4-Aminobenzonitrile → 4-(5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

HRID 1042271

反応式

HRID 1042271 の反応式
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[N:10]1[C:15]2[NH:16][CH:17]=[CH:18][C:14]=2[C:13]([C:19]2[C:20]([NH:25][C:26]3[C:27]4[CH:28]=[CH:29][N:30]=[C:31](Cl)[C:32]=4[CH:33]=[CH:34][C:35]=3[CH3:36])=[N:21][CH:22]=[CH:23][CH:24]=2)=[N:12][CH:11]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.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]>[N:10]1[C:15]2[NH:16][CH:17]=[CH:18][C:14]=2[C:13]([C:19]2[C:20]([NH:25][C:26]3[C:35]([CH3:36])=[CH:34][CH:33]=[C:32]4[C:27]=3[CH:28]=[CH:29][N:30]=[C:31]4[NH:1][C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=3)=[N:21][CH:22]=[CH:23][CH:24]=2)=[N:12][CH:11]=1

参加物

7

反応物 4

HCID 133964-AminobenzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 59627376N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine

生成物 1

HCID 251326674-(5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
120 °C

実験手順

A mixture of 4-aminobenzonitrile (35 mg, 299 mmol), N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine (110 mg, 284 μmol), tris(dibenzylideneacetone)dipalladium(0) (10 mg, 11 μmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (9 mg, 23 μmol) were suspended in THF (1 mL) and sealed. The mixture was sonicated until homogeneously mixed. Lithium bis(trimethylsilyl)amide (1.28 mL, 1280 mmol) was then added through a syringe, then mixed well with sonication. The reaction tube was heated via microwave to 120° C. for 15 min. The reaction mixture was cooled to room temperature, then partitioned between EtOAc (3×50 mL) and NaHCO3 (aq., sat). The organic layer was washed with brine, and extracted with HCl (aq., 1 N, 3×50 mL). The aqueous layers were combined and filtered through a layer of celite. The filter cake was rinsed with 1 N HCl. The filtrate was then cooled in ice and neutralized with NH4OH (aq., conc.) to pH 8, then extracted with EtOAc (4×50 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and then concentrated to give a brown solid which was then triturated with MeOH to give a light brown solid upon filtration. The filter cake was air dried over the weekend to give 4-(5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS (ESI, pos. ion) m/z: 469.2

後処理

  1. customsealed
  2. customThe mixture was sonicated
  3. additionuntil homogeneously mixed
  4. additionmixed well with sonication
  5. temperatureThe reaction mixture was cooled to room temperature
  6. custompartitioned between EtOAc (3×50 mL) and NaHCO3 (aq., sat)
  7. washThe organic layer was washed with brine
  8. extractionextracted with HCl (aq., 1 N, 3×50 mL)
  9. filtrationfiltered through a layer of celite
  10. washThe filter cake was rinsed with 1 N HCl
  11. temperatureThe filtrate was then cooled in ice and neutralized with NH4OH (aq., conc.) to pH 8
  12. extractionextracted with EtOAc (4×50 mL)
  13. washwashed with brine
  14. dry with materialdried over Na2SO4
  15. concentrationconcentrated
  16. customto give a brown solid which
  17. customwas then triturated with MeOH
  18. customto give a light brown solid
  19. filtrationupon filtration
  20. customdried over the weekend

出典と根拠

ORDレコード
ord-83496dde42b748eaa605099e5d576c5b
出典データセット
uspto-grants-2013_10
特許番号
US08557830B2

関連ノート

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