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Dichloromethane → (S)-methyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6-(7H)-carboxylate

HRID 1626680
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HRID 1626680 반응식
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]2[CH3:21])[C:5]2[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH2:22]([NH:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[C:30]([F:43])[CH:29]=1)=[O:26])[CH3:23].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>[CH2:22]([NH:24][C:25](=[O:26])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[N:3]=[C:4]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]3[CH3:21])[C:5]3[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=3[N:7]=2)=[C:30]([F:43])[CH:29]=1)[CH3:23]
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참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666787871-Ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2회HCID 86663170(S)-methyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2회

생성물 1

HCID 66678967
(S)-methyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6-(7H)-carboxylate
수율 4.2%

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 (S)-methyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 26) (98 mg, 0.313 mmol), 1-ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 28) (110 mg, 0.357 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (13 mg, 0.0157 mmol) and sodium carbonate (93 mg, 0.876 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 was re-dissolved in a mix of H2O and EtOAc. The aqueous phase was extracted into EtOAc and the organic extracts were combined and concentrated in vacuo. The sample was then purified via preparative HPLC at low pH and then triturated in MeOH and filtered to yield the title compound (6 mg, 4%).

후처리

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue was re-dissolved in
  3. additiona mix of H2O and EtOAc
  4. extractionThe aqueous phase was extracted into EtOAc
  5. concentrationconcentrated in vacuo
  6. customThe sample was then purified via preparative HPLC at low pH
  7. customtriturated in MeOH
  8. filtrationfiltered

출처 및 근거

ORD 기록
ord-2acafa66c7984fbba5a19901a92565d8
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08785457B2

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