Cesium carbonate → 2-(2-Amino-pyrimidin-4-yl)-3-(3-methoxy-phenylamino)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 869328Notes

Reaction equation

HRID 869328 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[CH3:49][O:50][C:51]1[CH:52]=[C:53]([NH2:57])[CH:54]=[CH:55][CH:56]=1.[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][C:68]2[N:71]([CH3:92])[C:72]([C:75]3[CH:80]=[CH:79][N:78]=[C:77]([N:81]4C(=O)C5C(=CC=CC=5)C4=O)[N:76]=3)=[C:73](I)[C:67]=2[C:66]1=[O:93])=[O:64])([CH3:61])([CH3:60])[CH3:59]>O1CCOCC1.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:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][C:68]2[N:71]([CH3:92])[C:72]([C:75]3[CH:80]=[CH:79][N:78]=[C:77]([NH2:81])[N:76]=3)=[C:73]([NH:57][C:53]3[CH:54]=[CH:55][CH:56]=[C:51]([O:50][CH3:49])[CH:52]=3)[C:67]=2[C:66]1=[O:93])=[O:64])([CH3:61])([CH3:60])[CH3:59]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 108243-MethoxyanilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 672851072-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pyrimidin-4-yl]-3-iodo-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 672853442-(2-Amino-pyrimidin-4-yl)-3-(3-methoxy-phenylamino)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl esterYield 23%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Cesium carbonate (0.154 g, 0.473 mmol), 4,5-bis(diphenylphoshino)-9,9-dimethylxanthene (0.027 g, 0.047 mmol), Pd2(dba)3 (0.0217 g, 0.023 mmol), 3-methoxy-phenylamine (0.038 g, 0.308 mmol) were added under argon to a solution of 2-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pyrimidin-4-yl]-3-iodo-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (0.142 mg, 0.237 mmol) in dry dioxane (4.0 ml) and the reaction mixture was stirred at 100° C. for 24 h under argon atmosphere. The solvent was removed under vacuum, the residue was taken up into DCM (5.0 ml), filtered, and the organic layer was washed with purite water (1×5.0 ml), dried over Na2SO4. The filtrate was purified over silica, using DCM/MeOH (9.5:0.5) as eluent, affording 2-(2-Amino-pyrimidin-4-yl)-3-(3-methoxy-phenylamino)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (0.025 g, 0.053 mmol, 23%).

Workup

  1. customThe solvent was removed under vacuum
  2. filtrationfiltered
  3. washthe organic layer was washed with purite water (1×5.0 ml)
  4. dry with materialdried over Na2SO4
  5. customThe filtrate was purified over silica

Sources & evidence

ORD record
ord-537db934785d46e7b781d3f980b74fa7
Source dataset
uspto-grants-2015_03
Patent number
US08969366B2

Reaction notes

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