Sodium Carbonate → 2-Amino-5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)-pyrimidin-4-yl]-isonicotinonitrile

HRID 1512136

反応式

HRID 1512136 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]#[N:9])[C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Br[C:20]1[N:25]=[C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:23]=[C:22]([NH:32][C:33]2[CH:34]=[N:35][C:36]3[C:41]([CH:42]=2)=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[NH2:1][C:2]1[CH:7]=[C:6]([C:5]([C:20]2[CH:21]=[C:22]([NH:32][C:33]3[CH:34]=[N:35][C:36]4[C:41]([CH:42]=3)=[CH:40][CH:39]=[CH:38][CH:37]=4)[N:23]=[C:24]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:25]=2)=[CH:4][N:3]=1)[C:8]#[N:9]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 595075092-Amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-4-carbonitrileHCID 59507540N-(6-bromo-2-morpholinopyrimidin-4-yl)quinolin-3-amine

生成物 1

HCID 595077342-Amino-5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)-pyrimidin-4-yl]-isonicotinonitrile収率 21.2%

試薬・触媒・溶媒 2

HCID 53485975CID 53485975触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To the crude 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-4-carbonitrile (prepared as in Method 11) (25 mg, 0.13 mmol) solution in dioxane (1.8 mL) in a pressure vessel, was added (6-bromo-2-morpholin-4-yl-pyrimidin-4-yl)-quinolin-3-yl-amine (19.4 mg, 0.05 mmol) and aq. Na2CO3 (2 M, 0.6 mL, 1.2 mmol). After purging the reaction mixture with argon, dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (10.3 mg, 0.01 mmol) was added in one portion. The pressure vessel was sealed and the mixture was heated in a microwave at 120° C. for 900 seconds. The crude mixture was filtered and concentrated under reduced pressure. The crude product was purified by reverse phase preparative HPLC to give 2-amino-5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)-pyrimidin-4-yl]-isonicotinonitrile (4.5 mg, 20%). LC/MS (m/z): 425.0 (MH+), Rt 2.03 minutes.

後処理

  1. additionwas added in one portion
  2. customThe pressure vessel was sealed
  3. filtrationThe crude mixture was filtered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-60d381057df44437bfbfcd3d9da6da70
出典データセット
uspto-grants-2012_07
特許番号
US08217035B2

関連ノート

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