Sodium Carbonate → HCID 54597166、化合物

HRID 2174662ノート

反応式

HRID 2174662 の反応式
[CH2:1]([O:8][C:9]1[C:10]([NH2:16])=[N:11][CH:12]=[C:13](Br)[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH:23]([N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]1=[O:41])([CH3:25])[CH3:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CCC=1>C(#N)C.Cl[Pd]Cl.[Fe].ClCCl>[NH2:16][C:10]1[N:11]=[CH:12][C:13]([C:30]2[CH:29]=[CH:28][C:27](=[O:41])[N:26]([CH:23]([CH3:25])[CH3:24])[CH:31]=2)=[N:14][C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

9

反応物 4

HCID 10340Sodium CarbonateHCID 3524393Cyclopenta-1,4-dien-1-yl(diphenyl)phosphaneHCID 107551623-(Benzyloxy)-5-bromopyrazin-2-amineHCID 580703861-Isopropyl-6-oxo-1,6-dihydropyridine-3-boronic Acid Pinacol Ester

生成物 1

HCID 54597166HCID 54597166、化合物収率 13.3%

試薬・触媒・溶媒 4

HCID 23925Iron触媒HCID 24290Palladium Chloride触媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

3-(benzyloxy)-5-bromopyrazin-2-amine (100 mg, 0.358 mmol) was dissolved in acetonitrile (4 mL). Aqueous Na2CO3 solution (462.3 μL of 2 M, 0.9247 mmol), 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (146.0 mg, 0.5548 mmol) and cyclopenta-1,4-dien-1-yl(diphenyl)phosphane; dichloromethane; dichloropalladium; iron (75.33 mg, 0.09247 mmol) was added and the reaction mixture was heated for 30 minutes at 100° C. under microwave conditions. The reaction mixture was concentrated in vacuo and the residue was partitioned between DCM and water. The layers were separated and the aqueous further extracted with DCM. The combined organic extract was dried (MgSO4), filtered and concentrated in vacuo. This material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, and freeze-dried to give the title compound (16 mg, 6.13% Yield). H1 NMR (400.0 MHz, DMSO) δ 1.35 (d, J=6.8 Hz, 6H), 5.10 (m, J=6.8 Hz, 1H), 5.53 (s, 2H), 6.46 (d, J=9.5 Hz, 1H), 7.32 (m, J=7.3 Hz, 1H), 7.38-7.41 (m, 2H), 7.54 (d, J=7.2 Hz, 2H), 7.95 (dd, J=2.5, 9.5 Hz, 1H), 7.98 (s, 1H) and 8.06 (d, J=2.5 Hz, 1H). MS (ES+) 337.0

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe layers were separated
  4. extractionthe aqueous further extracted with DCM
  5. extractionThe combined organic extract
  6. dry with materialwas dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThis material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  10. customThe fractions were collected
  11. customfreeze-dried

出典と根拠

ORDレコード
ord-b03129a4b43e4e9d97392930e316c033
出典データセット
uspto-grants-2015_06
特許番号
US09062008B2

反応ノート

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