HCID 53307538, compound → HCID 53307539, compound

HRID 1497316Notes

Reaction equation

HRID 1497316 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([NH:21][C@H:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]3[OH:28])=[O:20])[CH:10]=2)=[CH:4][CH:3]=1.[Zn](C)[CH3:30]>C1COCC1.C1(C)C=CC=CC=1.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]>[OH:28][C@H:23]1[CH2:24][CH2:25][CH2:26][CH2:27][C@@H:22]1[NH:21][C:19]([C:11]1[CH:10]=[C:9]([CH2:8][C:5]2[CH:6]=[N:7][C:2]([CH3:30])=[CH:3][CH:4]=2)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1)=[O:20]

Participants

6

Reactant 2

HCID 53307538HCID 53307538, compoundHCID 178477796HCID 178477796, compound2×

Product 1

HCID 53307539HCID 53307539, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of Example 1 (94 mg, 0.237 mmol) and PdCl2(dppf) (18 mg, 0.047 mmol) in THF (1 ml) at room temperature was added ZnMe2 in toluene (1.2 M, 0.4 mL). The reaction mixture was stirred at 50° C. for 2 h. A second portion of ZnMe2 (0.6 mL) and PdCl2(dppf) (18 mg) was added. The reaction was heated at 50° C. for 3 h, cooled and quenched by sat. aqueous NaHCO3. The mixture was extracted with EtOAc, dried over Na2SO4, filtered and concentrated. Purification by reverse-phase HPLC (C-18 column, 5-90% MeCN in H2O with both containing 0.05% TFA) provided the title compound. 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J=2.0 Hz, 1H), 8.27 (d, J=7.6 Hz, 1H), 8.13 (s, 1H), 8.13 (d, J=8.0 Hz, 1H), 8.02 (d, J=7.6 Hz, 1H), 7.75 (t, J=8.0 Hz, 1H), 7.60 (d, J=7.6, 1H), 7.30 (dd, J=2.4, 8.0 Hz, 1H), 7.04 (d, J=8.0 Hz, 2H), 4.45 (s, 2H), 3.92-3.84 (m, 1H), 3.61-3.57 (m, 1H), 2.51 (s, 3H), 2.17-2.12 (m, 2H), 1.82-1.79 (m, 2H), 1.54-1.23 (m, 4H). HRMS (ES) [M+1]+ calcd for C23H25N3O2: 376.2020, Found: 376.2010.

Workup

  1. temperatureThe reaction was heated at 50° C. for 3 h
  2. temperaturecooled
  3. customquenched by sat. aqueous NaHCO3
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by reverse-phase HPLC (C-18 column, 5-90% MeCN in H2O with both containing 0.05% TFA)

Sources & evidence

ORD record
ord-d21ccfe9fce64b1bb9b202d44bfe0196
Source dataset
uspto-grants-2015_12
Patent number
US09199939B2

Reaction notes

Loading…