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

HRID 1512136

반응식

HRID 1512136 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 53485975CID 53485975촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-60d381057df44437bfbfcd3d9da6da70
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217035B2

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