Dichloromethane → HCID 66937030、化合物

HRID 1963954ノート

反応式

HRID 1963954 の反応式
Cl[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)[CH:5]=[N:4][CH:3]=1.[Cl:16][C:17]1[C:18](B(O)O)=[CH:19][C:20]([F:23])=[N:21][CH:22]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>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].CO.C(OCC)(=O)C.COCCOC>[Cl:16][C:17]1[C:18]([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)[CH:5]=[N:4][CH:3]=2)=[CH:19][C:20]([F:23])=[N:21][CH:22]=1

参加物

9

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 534102886-Chloro-N-[(tetrahydro-2H-pyran-4-yl)methyl]-2-pyrazinamine

生成物 1

HCID 66937030HCID 66937030、化合物収率 49.8%

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 887Methanol溶媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (1390 mg, 6.10 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (2141 mg, 12.21 mmol), PdCl2(dppf).CH2Cl2 adduct (399 mg, 0.488 mmol), DME (24 ml) and 2M sodium carbonate (9.16 ml, 18.31 mmol) was stirred atl 10-115° C. for 90 min and the reaction progress was followed by LCMS. The reaction mixture was cooled, 30 ml of ethyl acetate and 20 ml of methanol were added, filtered and concentrated to crude product. The crude was purified by silica gel chromatography using 80 g column eluting with 20-75% ethyl acetate in heptane. The desired fractions were concentrated to constant mass, giving 980 mg of titled compound as free base. LCMS (m/z): 323.0 (MH+), retention time=0.81 min.

後処理

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. concentrationconcentrated to crude product
  4. customThe crude was purified by silica gel chromatography
  5. washeluting with 20-75% ethyl acetate in heptane
  6. concentrationThe desired fractions were concentrated to constant mass

出典と根拠

ORDレコード
ord-369d8ccd879141338a284083dd4b3a02
出典データセット
uspto-grants-2013_04
特許番号
US08415381B2

反応ノート

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