Potassium Phosphate, Tribasic → 2-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(5-carbamoyl-1-methyl-1H-pyrrol-3-yl)benzyl acetate

HRID 1025579Notes

Reaction equation

HRID 1025579 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([NH2:10])=[O:9])[N:5]([CH3:7])[CH:6]=1.[C:11]([O:14][CH2:15][C:16]1[C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:19]=[CH:18][C:17]=1[N:31]1[N:40]([CH3:41])[CH2:39][C:38]2[C:33](=[CH:34][CH:35]=[C:36]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:37]=2)[C:32]1=[O:46])(=[O:13])[CH3:12].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.O1CCOCC1>[C:11]([O:14][CH2:15][C:16]1[C:21]([C:2]2[CH:3]=[C:4]([C:8](=[O:9])[NH2:10])[N:5]([CH3:7])[CH:6]=2)=[CH:20][CH:19]=[CH:18][C:17]=1[N:31]1[N:40]([CH3:41])[CH2:39][C:38]2[C:33](=[CH:34][CH:35]=[C:36]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:37]=2)[C:32]1=[O:46])(=[O:13])[CH3:12]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 434111534-bromo-1-methyl-1H-pyrrole-2-carboxylic acid amideHCID 710087262-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate

Product 1

HCID 710081532-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(5-carbamoyl-1-methyl-1H-pyrrol-3-yl)benzyl acetateYield 16%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

In a 10 ml microwave vial, 4-bromo-1-methyl-1H-pyrrole-2-carboxamide (82.5 mg, 406 μmol, Eq: 1.00), [prepared in Example 12, Step 1], 2-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (200 mg, 406 μmol, Eq: 1.00), X-phos (19.4 mg, 40.6 μmol, Eq: 0.10), and potassium phosphate tribasic (259 mg, 1.22 mmol, Eq: 3.00) were combined with 1,4-dioxane (5 ml) and water (0.5 ml) to give a dark brown suspension. The reaction mixture was stirred while purging with argon for 10 min. The reaction mixture was heated at 125° C. in the microwave for 30 min. The reaction mixture was diluted with 50 mL of dichloromethane and dried (MgSO4). Concentrated in vacuo. The crude material was purified by flash chromatography (silica, 20%-100% ethyl acetate/hexanes gradient) to give 2-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(5-carbamoyl-1-methyl-1H-pyrrol-3-yl)benzyl acetate (31 mg, 16%): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 9H) 1.98 (s, 3H) 2.68 (s, 3H) 3.99 (s, 2H) 5.28 (s, 2H) 6.72 (d, J=1.89 Hz, 1H) 6.84-6.94 (m, 1H) 7.23 (d, J=1.51 Hz, 1H) 7.27-7.52 (m, 5H) 7.61 (s, 1H) 8.04 (d, J=7.93 Hz, 1H).

Workup

  1. customto give a dark brown suspension
  2. customwhile purging with argon for 10 min
  3. additionThe reaction mixture was diluted with 50 mL of dichloromethane
  4. dry with materialdried (MgSO4)
  5. concentrationConcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica, 20%-100% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-e9e0cc40877e48d0932d4fac2fb31baa
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

Loading…