Potassium Phosphate, Tribasic → HCID 58631240, 화합물

HRID 1612370

반응식

HRID 1612370 반응식
Br[C:2]1[N:3]=[CH:4][C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[O:8][CH3:9].C1(P(C2CCCCC2)C2C=CC=CC=2C2C3C(C4C=CC=CC=4C=2)=CC=CC=3)CCCCC1.[Cl:54][C:55]1[CH:60]=[C:59]([Cl:61])[CH:58]=[CH:57][C:56]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:54][C:55]1[CH:60]=[C:59]([Cl:61])[CH:58]=[CH:57][C:56]=1[C:2]1[N:3]=[CH:4][C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[O:8][CH3:9]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2734659(2,4-Dichlorophenyl)boronic acid4회HCID 22147288Dicyclohexyl(2-(phenanthren-9-yl)phenyl)phosphaneHCID 58631232HCID 58631232, 화합물

생성물 1

HCID 58631240HCID 58631240, 화합물수율 31%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매4회HCID 1140Toluene용매HCID 6344Dichloromethane용매

반응 조건

온도
110 °C

실험 절차

A Kimble vial was charged with (1R,2S)-1-[(5-bromo-6-methoxypyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol (0.55 g, 1.63 mmol), Pd2(dba)3 (33 mg, 35 μmol), dicyclohexyl[2-(9-phenanthryl)phenyl]phosphine (64 mg), 2,4-dichlorophenylboronic acid (567 mg, 2.67 mmol), K3PO4 (1.13 g, 5.34 mmol) and toluene (15 mL). The vial was flushed with N2, sealed and heated at 110° C. for 6 hr. Cool to rt, add additional Pd2(dba)3 (33 mg) and 2,4-dichlorophenylboronic acid (0.5 g, 2.7 mmol). Continue heating overnight. Add additional Pd2(dba)3 (33 mg) and 2,4-dichlorophenylboronic acid (0.5 g, 2.7 mmol) and continue heating for 5 hr. Add additional Pd2(dba)3 (33 mg) and 2,4-dichlorophenylboronic acid (0.5 g, 2.7 mmol) and continue heating overnight. The reaction was cooled to rt, diluted with CH2Cl2, washed with sat. aq NaHCO3 and sat. aq. NaCl. Dry organic extract over MgSO4, filter and concentrate. Purify by biotage MPLC (90 g column, 30% ethyl acetate/hexanes) to afford 0.2 g (31%) of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-6-methoxypyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol as an oil: 1H NMR (CDCl3) δ 3.06-3.10, 3.26-3.32, 3.92, 4.79, 5.33, 5.49-5.50, 7.28-7.41, 7.50, 7.74; MS (ESI+) for C20H17Cl2N3O2 m/z 402 (M+H)+.

후처리

  1. customThe vial was flushed with N2
  2. customsealed
  3. temperatureCool to rt
  4. temperatureContinue heating overnight
  5. temperaturecontinue heating for 5 hr
  6. temperaturecontinue heating overnight
  7. temperatureThe reaction was cooled to rt
  8. washwashed with sat. aq NaHCO3 and sat. aq. NaCl
  9. extractionDry organic extract over MgSO4
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify by biotage MPLC (90 g column, 30% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-71b5a4ae7355448d80c2f5a4b7a749ce
출처 데이터셋
uspto-grants-2006_01
특허 번호
US06992087B2

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