Acetic Acid → HCID 66604576, compound

HRID 2410876Notes

Reaction equation

HRID 2410876 reaction equation
[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])=[CH:19][CH:18]=2)=[C:12]([CH:15]=1)[C:13]#[N:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=[O:33])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([C:8]1[CH:15]=[C:12]([C:13]([NH2:14])=[O:33])[C:11]2[NH:16][C:17]3[C:22]([C:10]=2[CH:9]=1)=[CH:21][C:20]([C:23]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[O:24])=[CH:19][CH:18]=3)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 66604798HCID 66604798, compound

Product 1

HCID 66604576HCID 66604576, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
130 °C

Procedure

A 5-ml microwave vial was loaded with 5-benzyl-2-(4-(morpholine-4-carbonyl)phenylamino)benzonitrile (42 mg, 0.080 mmol), acetic acid (4 mL) and palladium acetate (45.1 mg, 0.201 mmol). The flask was sealed and heated to 130° C. for 13 hours. The reaction mixture was filtered through a 0.45 um Nylon filter and concentrated in vacuum. The crude was filtered through a layer of BIOTAGE® Si-propylthiol resin (0.8 g in a 6 ml cartridge, to remove Pd) and rinsed with methanol. The pale yellow eluent was concentrated and purified by prep HPLC to give 7.0 mg 3-benzyl-6-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide. MS (ESI) m/e−412, m/e+=414 consistent with [M−H]− and [M+H]+ resp. HPLC retention time 9.14 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA). 1H NMR (CD3OD) δ ppm 8.18 (m, 2H), 7.87 (s, 1H), 7.65 (b, 1H), 7.52 (b, 1H), 7.30 (m, 4H), 7.20 (b, 1H), 4.21 (s, 2H), 3.90-3.50 (b, 8H).

Workup

  1. customThe flask was sealed
  2. filtrationThe reaction mixture was filtered through a 0.45 um Nylon
  3. filtrationfilter
  4. concentrationconcentrated in vacuum
  5. filtrationThe crude was filtered through a layer of BIOTAGE® Si-propylthiol resin (0.8 g in a 6 ml cartridge
  6. customto remove Pd) and
  7. washrinsed with methanol
  8. concentrationThe pale yellow eluent was concentrated
  9. custompurified by prep HPLC

Sources & evidence

ORD record
ord-965b1f6e99b249abbb80dd24c0f4defb
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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