Dichloromethane → Methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

HRID 1626698노트

반응식

HRID 1626698 반응식
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[C:30]([F:43])[CH:29]=2)=[O:26])[CH2:23][CH2:22]1.ClCCl.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].CCO.O.COCCOC>[CH:21]1([NH:24][C:25](=[O:26])[NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:2]3[N:3]=[C:4]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]4[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=4[N:7]=3)=[C:30]([F:43])[CH:29]=2)[CH2:22][CH2:23]1

참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666792291-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2회HCID 86663169methyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2회

생성물 1

HCID 66678810Methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate수율 22%

시약·촉매·용매 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

A solution of methyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 25) (10 mg, 0.335 mol), 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (122 mg, 0.382 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (14 mg, 0.0168 mmol) and sodium carbonate (107 mg, 1.01 mmol) in 2 ml of a 7:3:1 mixture of DME:H2O:EtOH respectively was heated in the microwave at 115° C. for 45 minutes. The reaction was concentrated in vacuo and the residue redissolved in a mix of MeOH/DCM. It was loaded onto an SCX cartridge and washed with two column volumes of MeOH/DCM before being eluted with 2M NH3 in MeOH and concentrated in vacuo. The sample was then purified via preparative HPLC at low pH to yield the title compound (33 mg, 22%).

후처리

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue redissolved in
  3. additiona mix of MeOH/DCM
  4. washwashed with two column volumes of MeOH/DCM
  5. washbefore being eluted with 2M NH3 in MeOH
  6. concentrationconcentrated in vacuo
  7. customThe sample was then purified via preparative HPLC at low pH

출처 및 근거

ORD 기록
ord-d1ed7572b7554c23a3ab8595bb820789
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785457B2

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