Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl) pyrazin-2-amine

HRID 1623388ノート

反応式

HRID 1623388 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:6][C:7]=1[C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([F:15])[CH:9]=1.[C:24]([O-])([O-])=O.[Na+].[Na+].CB(O)O.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:14][C:13]1[C:8]([C:7]2[N:6]=[C:5]([NH:16][CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH:4]=[N:3][C:2]=2[CH3:24])=[CH:9][C:10]([F:15])=[N:11][CH:12]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 866506355-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

生成物 1

HCID 669368756-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl) pyrazin-2-amine収率 75%

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
105 °C

実験手順

To a degassed suspension of 5-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (10 mg, 0.028 mmol), Na2CO3 (0.036 ml, 2 M, 0.072 mmol) and methylboronic acid (5 mg, 0.084 mmol) in DME (1 ml) was added PdCl2(dppf).CH2Cl2 adduct (6 mg, 7.35 μmol). The reaction was capped and heated to 105° C. for 4 hr an oil bath. The reaction 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 (50% EtOAc/Hexane) to yield 6-(5-chloro-2-fluoropyridin-4-yl)-5-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (7 mg, 0.021 mmol, 74.2% yield). LCMS (m/z): 337.2 (MH+), retention time=0.81 min.

後処理

  1. customThe reaction was capped
  2. washwashed with H2O
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by column chromatography on silica gel (50% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-ec73363d320e46d88d70ef91df727b61
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

反応ノート

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