Pyridine → 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

HRID 869327Notes

Reaction equation

HRID 869327 reaction equation
[C:1](Cl)(=[O:11])[C:2]1[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=1)[C:4](Cl)=[O:5].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]2[N:26]([CH3:37])[C:27]([C:30]3[CH:35]=[CH:34][N:33]=[C:32]([NH2:36])[N:31]=3)=[C:28]([I:29])[C:22]=2[C:21]1=[O:38])=[O:19])([CH3:16])([CH3:15])[CH3:14].N1C=CC=CC=1>C(Cl)Cl>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]2[N:26]([CH3:37])[C:27]([C:30]3[CH:35]=[CH:34][N:33]=[C:32]([N:36]4[C:4](=[O:5])[C:3]5[C:2](=[CH:10][CH:9]=[CH:8][CH:7]=5)[C:1]4=[O:11])[N:31]=3)=[C:28]([I:29])[C:22]=2[C:21]1=[O:38])=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6955Phthaloyl chlorideHCID 672843262-(2-Amino-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 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 esterYield 74.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Pthaloyl chloride (0.089 g, 0.437 mmol) was added to a cold (0° C.) solution of 2-(2-Amino-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 (prepared as described in Example 1) (0.158 g, 0.337 mmol) and pyridine (0.069 g, 0.875 mmol) in dry DCM (1.5 ml) and the reaction mixture was stirred at room temperature in argon atmosphere for 4 h. The organic layer was washed with a saturated solution of NaHCO3 (1×2.0 ml), brine (1×2.0 ml), and it was dried over Na2SO4. The filtrate was evaporated to dryness to give the crude product, which was purified by flash chromatography, over silica gel (DCM/MeOH (9.8:0.2) as eluent), to afford 2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyrimidin-4-yl]-3-iodo-1-methyl-4-oxo-1,4,6,7-tetra-hydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (0.150 mg, 0.25 mmol, 74%).

Workup

  1. washThe organic layer was washed with a saturated solution of NaHCO3 (1×2.0 ml), brine (1×2.0 ml), and it
  2. dry with materialwas dried over Na2SO4
  3. customThe filtrate was evaporated to dryness
  4. customto give the crude product, which
  5. customwas purified by flash chromatography, over silica gel (DCM/MeOH (9.8:0.2) as eluent)

Sources & evidence

ORD record
ord-9aaec7630235446bbf574d4bea04d313
Source dataset
uspto-grants-2015_03
Patent number
US08969366B2

Reaction notes

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