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Potassium Phosphate, Tribasic → tert-Butyl 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

HRID 521215
ノート
印刷プレビュー

反応式

HRID 521215 の反応式
[NH2:1][C:2]1[C:6]([C:7](=[O:9])[NH2:8])=[CH:5][N:4]([C:10]2([CH2:23][C:24]#[N:25])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[N:3]=1.Br[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([F:33])[CH:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CCOC(C)=O.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].O1CCOCC1>[C:7]([C:6]1[C:2]([NH:1][C:27]2[CH:32]=[CH:31][N:30]=[C:29]([F:33])[CH:28]=2)=[N:3][N:4]([C:10]2([CH2:23][C:24]#[N:25])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:12][CH2:11]2)[CH:5]=1)(=[O:9])[NH2:8]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 27628514-Bromo-2-fluoropyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86729368tert-Butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate2 回

生成物 1

HCID 71536249tert-Butyl 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
95 °C

実験手順

To a microwave vial was added tert-butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (Intermediate 35-1) (5.0 g, 14 mmol), 4-bromo-2-fluoropyridine (2.5 g, 14 mmol), K3PO4 (6.1 g, 29 mmol), and dioxane (72 mL). The mixture was degassed with bubbling argon for 5 minutes. Pd2(dba)3 (0.7 g, 0.7 mmol) and X-Phos (1.0 g, 2.2 mmol) were then added, and the vial was sealed and heated to 95° C. for 5 hours. The mixture was then cooled to ambient temperature, diluted with EtOAc, filtered through celite, and eluted with EtOAc. The filtrate was concentrated in vacuo, and the resulting yellow oil was purified by MPLC on silica gel (using a gradient elution of 50-100% EtOAc/hexanes) to afford the title compound, Example #9-1.

後処理

  1. customThe mixture was degassed with bubbling argon for 5 minutes
  2. customthe vial was sealed
  3. temperatureThe mixture was then cooled to ambient temperature
  4. filtrationfiltered through celite
  5. washeluted with EtOAc
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe resulting yellow oil was purified by MPLC on silica gel (
  8. washa gradient elution of 50-100% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-93d2efe1636746b78344f76323a87168
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09328099B2

反応ノート

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