Potassium Phosphate, Tribasic → HCID 58631240、化合物

HRID 1824285

反応式

HRID 1824285 の反応式
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]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2734659(2,4-Dichlorophenyl)boronic acid4 回HCID 22147288Dicyclohexyl(2-(phenanthren-9-yl)phenyl)phosphaneHCID 58631232HCID 58631232、化合物

生成物 1

HCID 58631240HCID 58631240、化合物収率 31%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒4 回HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
110 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-fa40eef091624b7f9555f45b80caf6d5
出典データセット
uspto-grants-2006_05
特許番号
US07041672B2

関連ノート

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