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

HRID 1512135노트

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HRID 1512135 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 178418807HCID 178418807, 화합물촉매

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온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-37655cdb155e4ef8ac1cb26a76d275a7
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217035B2

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