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

HRID 1662805Notes

Reaction equation

HRID 1662805 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([Cl:17])=[C:12]([CH:16]=1)[C:13]([OH:15])=O)=[O:6].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[N:39]1([CH2:44][CH2:45][CH2:46][S:47]([C:50]2[CH:55]=[CH:54][C:53]([NH:56][C:57]3[N:62]=[CH:61][C:60]([NH2:63])=[CH:59][N:58]=3)=[CH:52][CH:51]=2)(=[O:49])=[O:48])[CH2:43][CH2:42][CH2:41][CH2:40]1>C(Cl)Cl.CN(C=O)C>[Cl:17][C:11]1[CH:10]=[CH:9][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:18]=[CH:19][CH:20]=[C:2]([CH3:1])[CH:3]=2)=[CH:16][C:12]=1[C:13]([NH:63][C:60]1[CH:61]=[N:62][C:57]([NH:56][C:53]2[CH:54]=[CH:55][C:50]([S:47]([CH2:46][CH2:45][CH2:44][N:39]3[CH2:43][CH2:42][CH2:41][CH2:40]3)(=[O:48])=[O:49])=[CH:51][CH:52]=2)=[N:58][CH:59]=1)=[O:15]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 286666905-(3-Methylbenzamido)-2-Chlorobenzoic AcidHCID 58748692N-[4-(3-Pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-pyrimidine-2,5-diamine

Product 1

HCID 249603662-Chloro-5-(3-Methyl-Benzoylamino)-N-{2-[4-(3-Pyrrolidin-1-yl-Propane-1-Sulfonyl)-Phenylamino]-Pyrimidin-5-yl}-BenzamideYield 44.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of intermediate 4 (Example 7) (290 mg, 1 mmol) in anhydrous CH2Cl2 (30 mL), 2-chloro-4,6-dimethoxy-1,3,5-triazine (210 mg, 1.2 mmol) and 4-methylmorpholine (300 mg, 3 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 (85 mg, 13%).

Workup

  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

Sources & evidence

ORD record
ord-f4e08b0c767845fdb1b9f8109c374b15
Source dataset
uspto-grants-2011_10
Patent number
US08030487B2

Reaction notes

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