Sodium Carbonate → N-(6-(6-amino-4-fluoropyridin-3-yl)-2-morpholinopyrimidin-4-yl)quinolin-3-amine

HRID 1512135ノート

反応式

HRID 1512135 の反応式
[F:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][N:5]=[C:4]([NH2:17])[CH:3]=1.O1CCOCC1.Br[C:25]1[N:30]=[C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[N:28]=[C:27]([NH:37][C:38]2[CH:39]=[N:40][C:41]3[C:46]([CH:47]=2)=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH:26]=1.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].ClCCl>[NH2:17][C:4]1[N:5]=[CH:6][C:7]([C:25]2[N:30]=[C:29]([N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)[N:28]=[C:27]([NH:37][C:38]3[CH:39]=[N:40][C:41]4[C:46]([CH:47]=3)=[CH:45][CH:44]=[CH:43][CH:42]=4)[CH:26]=2)=[C:2]([F:1])[CH:3]=1

参加物

6

反応物 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 592518054-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinamineHCID 59507540N-(6-bromo-2-morpholinopyrimidin-4-yl)quinolin-3-amine

生成物 1

HCID 59507835N-(6-(6-amino-4-fluoropyridin-3-yl)-2-morpholinopyrimidin-4-yl)quinolin-3-amine収率 26%

試薬・触媒・溶媒 1

HCID 178418807HCID 178418807、化合物触媒

反応条件

温度
120 °C

実験手順

To a solution of 4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (prepared as shown in Method 10) in dioxane (1.7 mL, 0.13 mmol), N-(6-bromo-2-morpholinopyrimidin-yl)quinolin-3-amine (20 mg, 0.052 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (11 mg, 0.013 mmol) and 2 M aqueous sodium carbonate solution (0.6 mL, 1.2 mmol) were added under argon. The pressure vessel was sealed and the reaction mixture was heated in a microwave reactor at 120° C. for 15 minutes. The crude product was partitioned between EtOAc (30 mL) and saturated sodium bicarbonate (10 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by reverse phase preparative HPLC to give N-(6-(6-amino-4-fluoropyridin-3-yl)-2-morpholinopyrimidin-4-yl)quinolin-3-amine as yellow powder (14 mg, 26%). LC/MS (m/z): 418.0 (MH+), Rt 2.31 minutes.

後処理

  1. customThe pressure vessel was sealed
  2. customThe crude product was partitioned between EtOAc (30 mL) and saturated sodium bicarbonate (10 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-37655cdb155e4ef8ac1cb26a76d275a7
出典データセット
uspto-grants-2012_07
特許番号
US08217035B2

反応ノート

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