Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine

HRID 1623386

反応式

HRID 1623386 の反応式
Br[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:5]([NH2:16])=[N:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[Cl:23][C:24]1[C:25](B(O)O)=[CH:26][C:27]([F:30])=[N:28][CH:29]=1.C(Cl)Cl>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:23][C:24]1[C:25]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:5]([NH2:16])=[N:4][CH:3]=2)=[CH:26][C:27]([F:30])=[N:28][CH:29]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86626394HCID 86626394、化合物

生成物 1

HCID 669371366-(5-chloro-2-fluoropyridin-4-yl)-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine収率 29%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

To a degassed suspension of 6-bromo-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine (100 mg, 0.348 mmol), Na2CO3 (96 mg, 0.905 mmol) and 5-chloro-2-fluoropyridin-4-ylboronic acid (92 mg, 0.522 mmol) in DME (3 ml) was added PdCl2(dppf).CH2Cl2 adduct (22.75 mg, 0.028 mmol). The reaction mixture was capped in a flask and heated to 100° C. for 4 hr an oil bath. The reaction mixture was diluted with EtOAc and washed with H2O, sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude was purified by column chromatography on silica gel (100% EtOAc/Hexane) to yield 6-(5-chloro-2-fluoropyridin-4-yl)-N2-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2,3-diamine (34 mg, 0.101 mmol, 28.9% yield).). LCMS (m/z): 338.2 (MH+), retention time=0.65 min.

後処理

  1. customThe reaction mixture was capped in a flask
  2. washwashed with H2O
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by column chromatography on silica gel (100% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-6216497d72b34c3a995dc7cf72c4b8c4
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

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