Potassium Phosphate, Tribasic → 2-(tert-butylamino)-3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinazolin-4(3H)-one

HRID 1056323Notes

Reaction equation

HRID 1056323 reaction equation
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+].CC1(C)C(C)(C)OB([C:51]2[NH:59][C:58]3[CH2:57][CH2:56][NH:55][C:54](=[O:60])[C:53]=3[CH:52]=2)O1.[C:62]([NH:66][C:67]1[N:76]([CH3:77])[C:75](=[O:78])[C:74]2[C:69](=[C:70](I)[CH:71]=[CH:72][CH:73]=2)[N:68]=1)([CH3:65])([CH3:64])[CH3:63]>O1CCOCC1.O.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]>[C:62]([NH:66][C:67]1[N:76]([CH3:77])[C:75](=[O:78])[C:74]2[C:69](=[C:70]([C:51]3[NH:59][C:58]4[CH2:57][CH2:56][NH:55][C:54](=[O:60])[C:53]=4[CH:52]=3)[CH:71]=[CH:72][CH:73]=2)[N:68]=1)([CH3:65])([CH3:64])[CH3:63]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 897821382-(tert-butylamino)-8-iodo-3-methylquinazolin-4(3H)-oneHCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-one

Product 1

HCID 897836812-(tert-butylamino)-3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinazolin-4(3H)-oneYield 31%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of Xphos (12 mg, 0.027 mmol), Pd2dba3 (12 mg, 0.013 mmol), K3PO4 (169 mg, 0.80 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (609) (139 mg, 0.53 mmol) and 2-(tert-butylamino)-8-iodo-3-methylquinazolin-4(3H)-one (701) (95 mg, 0.27 mmol) in dioxane (2 mL), water (0.4 mL) in a sealed glass tube was heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc.) at 105° C. for 30 min. It was partitioned between 15 mL of EtOAc and 2 mL of 0.5 N NaOH. The organic layer was separated and concentrated under reduced pressure. The crude material was purified on a silica gel column (eluted with a gradient of 1-10% MeOH in DCM) to afford 2-(tert-butylamino)-3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinazolin-4(3H)-one (30 mg, 31% yield) as an off-white crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.00 (1H, br.), 7.94 (1H, dd, J=7.5, 1.5 Hz), 7.86 (1H, dd, J=7.8, 1.4 Hz), 7.18 (1H, t, J=7.6 Hz), 6.94 (2H, d, J=2.2 Hz), 5.98 (1H, s), 3.50 (3H, s), 3.44 (2H, m), 2.86 (2H, t, J=6.8 Hz), 1.56 (9H, s). m/z (ESI, +ve ion) 366.2 (M+H)+.

Workup

  1. customIt was partitioned between 15 mL of EtOAc and 2 mL of 0.5 N NaOH
  2. customThe organic layer was separated
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified on a silica gel column (
  5. washeluted with a gradient of 1-10% MeOH in DCM)

Sources & evidence

ORD record
ord-2eedd495d3b34792bdbb44991665dd11
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…