Potassium Phosphate, Tribasic → Benzyl 4-(3-{[3-(2-tert-butoxy-2-oxoethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-7-yl]carbonyl}-2-methylindolizin-1-yl)benzoate

HRID 1502217Notes

Reaction equation

HRID 1502217 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:29]1[C:30]([CH3:60])=[C:31]([C:38]([C:40]2[CH:49]=[C:48]3[C:43]([C:44](=[O:59])[N:45]([CH2:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:46](=[O:50])[NH:47]3)=[CH:42][CH:41]=2)=[O:39])[N:32]2[C:37]=1[CH:36]=[CH:35][CH:34]=[CH:33]2.OS([O-])(=O)=O.[K+]>CN(C=O)C.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]>[C:55]([O:54][C:52](=[O:53])[CH2:51][N:45]1[C:44](=[O:59])[C:43]2[C:48](=[CH:49][C:40]([C:38]([C:31]3[N:32]4[C:37]([CH:36]=[CH:35][CH:34]=[CH:33]4)=[C:29]([C:14]4[CH:15]=[CH:16][C:11]([C:9]([O:8][CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[O:10])=[CH:12][CH:13]=4)[C:30]=3[CH3:60])=[O:39])=[CH:41][CH:42]=2)[NH:47][C:46]1=[O:50])([CH3:58])([CH3:56])[CH3:57]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 516920Potassium bisulfateHCID 27732514-(Benzyloxycarbonyl)phenylboronic AcidHCID 131734308tert-butyl {7-[(1-bromo-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate

Product 1

HCID 89657670Benzyl 4-(3-{[3-(2-tert-butoxy-2-oxoethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-7-yl]carbonyl}-2-methylindolizin-1-yl)benzoateYield 92%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

{4-[(Benzyloxy)carbonyl]phenyl}boronic acid (0.7 g, 2.73 mmol), 5.5 mL of a molar solution of potassium phosphate and the catalyst PdCl2(dppf) (192 mg, 0.27 mmol) are added to a solution of tert-butyl {7-[(1-bromo-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate [described in Step 3.2.] (1 g, 1.82 mmol) in 20 mL of DMF placed in a microwave reactor under nitrogen. The reactor is sealed and the solution is heated for 30 min at 80° C. in a microwave. The reaction medium is cooled and run into a molar solution of KHSO4, and extracted with EtOAc. The organic phase is washed with a saturated aqueous solution of NaCl, dried over Na2SO4, and concentrated to dryness. The residue obtained is purified by flash chromatography on silica (DCM/EtOH: 100/0 to 80/20] to give 1.08 mg (92%) of a yellow solid.

Workup

  1. customplaced in a microwave reactor under nitrogen
  2. customThe reactor is sealed
  3. temperatureThe reaction medium is cooled
  4. extractionextracted with EtOAc
  5. washThe organic phase is washed with a saturated aqueous solution of NaCl
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. customThe residue obtained
  9. customis purified by flash chromatography on silica (DCM/EtOH

Sources & evidence

ORD record
ord-58194a709d4a4c1392cb8275620f643f
Source dataset
uspto-grants-2015_12
Patent number
US09206177B2

Reaction notes

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