Dichloromethane → (S)-1-cyclopropyl-3-(3-fluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea

HRID 1626676노트

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HRID 1626676 반응식
Cl[C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[C:5]2[CH2:10][N:9]([CH3:11])[CH2:8][C:6]=2[N:7]=1.[CH:19]1([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[C:28]([F:41])[CH:27]=2)=[O:24])[CH2:21][CH2:20]1.ClCCl.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.CCO.O.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]>[CH:19]1([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:2]3[N:3]=[C:4]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]4[CH3:18])[C:5]4[CH2:10][N:9]([CH3:11])[CH2:8][C:6]=4[N:7]=3)=[C:28]([F:41])[CH:27]=2)=[O:24])[CH2:21][CH2:20]1

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 666792291-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2회HCID 86663154(S)-4-(2-chloro-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine2회

생성물 1

HCID 66679048(S)-1-cyclopropyl-3-(3-fluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea수율 11%

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 86587095Dimethoxyethane ethanol water용매

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온도
115 °C

실험 절차

To a solution of (S)-4-(2-chloro-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 12) (150 mg, 0.55 mmol) and 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (212 mg, 0.69 mmol) in DME/EtOH/H2O (7/3/2) (2 mL) was added [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (22 mg, 0.027 mmol) and Cs2CO3 (538 mg, 1.65 mmol). The reaction mixture was then heated by microwave at 115° C. for 45 min. The crude reaction mixture was partitioned between EtOAc (25 ml) and water (25 ml). The organic layer was recovered, passed through a hydrophobic frit and the solvent removed in vacuo. Residue was then purified by preparative HPLC at low pH to afford a yellow solid (25 mg, 0.06 mmol, 11%).

후처리

  1. customThe crude reaction mixture
  2. customwas partitioned between EtOAc (25 ml) and water (25 ml)
  3. customThe organic layer was recovered
  4. customthe solvent removed in vacuo
  5. customResidue was then purified by preparative HPLC at low pH

출처 및 근거

ORD 기록
ord-c036a9900a7d4a54a46543dd7f8ae3aa
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785457B2

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