4-Methylmorpholine → 2-Methyl-N-{2-[4-(3-Pyrrolidin-1-yl-Propane-1-Sulfonyl)-Phenylamino]-Pyrimidin-5-yl}-5-(3-Trifluoromethyl-Benzoylamino)-Benzamide

HRID 1662803노트

반응식

HRID 1662803 반응식
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][CH:21]=1)[C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:18])=[C:13]([CH:17]=1)[C:14]([OH:16])=O)=[O:7].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[N:42]1([CH2:47][CH2:48][CH2:49][S:50]([C:53]2[CH:58]=[CH:57][C:56]([NH:59][C:60]3[N:65]=[CH:64][C:63]([NH2:66])=[CH:62][N:61]=3)=[CH:55][CH:54]=2)(=[O:52])=[O:51])[CH2:46][CH2:45][CH2:44][CH2:43]1>C(Cl)Cl.CN(C=O)C>[CH3:18][C:12]1[CH:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:19]=[CH:20][CH:21]=[C:3]([C:2]([F:1])([F:23])[F:22])[CH:4]=2)=[CH:17][C:13]=1[C:14]([NH:66][C:63]1[CH:64]=[N:65][C:60]([NH:59][C:56]2[CH:57]=[CH:58][C:53]([S:50]([CH2:49][CH2:48][CH2:47][N:42]3[CH2:46][CH2:45][CH2:44][CH2:43]3)(=[O:51])=[O:52])=[CH:54][CH:55]=2)=[N:61][CH:62]=1)=[O:16]

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 58748692N-[4-(3-Pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-pyrimidine-2,5-diamineHCID 596527072-Methyl-5-{[3-(trifluoromethyl)benzoyl]amino}benzoic acid

생성물 1

HCID 249599952-Methyl-N-{2-[4-(3-Pyrrolidin-1-yl-Propane-1-Sulfonyl)-Phenylamino]-Pyrimidin-5-yl}-5-(3-Trifluoromethyl-Benzoylamino)-Benzamide수율 15%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of intermediate 3 (Example 5) (170 mg, 0.5 mmol) in anhydrous CH2Cl2 (8 mL), 2-chloro-4,6-dimethoxy-1,3,5-triazine (100 mg, 0.6 mmol) and 4-methylmorpholine (210 mg, 2 mmol) were added. After the reaction mixture was stirred at room temperature for 75 minutes, intermediate 2 (Example 3) (100 mg, 0.3 mmol) in anhydrous DMF (2.5 mL) was added into the solution. The solution was stirred under argon for overnight. The residue was dissolved in CH2Cl2 (20 mL) and washed with aqueous saturated NaHCO3 solution (20 mL). The aqueous layer was extracted with CH2Cl2 (50 mL). The combined organic phase was dried (Na2SO4) and the solvent was removed. The crude product was purified by silica gel column with CHCl3 to 10% CH3OH/CHCl3 as eluents to give the final product as a white solid (27 mg, 15%).

후처리

  1. stirringThe solution was stirred under argon for overnight
  2. washwashed with aqueous saturated NaHCO3 solution (20 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (50 mL)
  4. dry with materialThe combined organic phase was dried (Na2SO4)
  5. customthe solvent was removed
  6. customThe crude product was purified by silica gel column with CHCl3 to 10% CH3OH/CHCl3 as eluents

출처 및 근거

ORD 기록
ord-4758007c50834b4893f8f70287e36ee0
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030487B2

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