Hydrochloric Acid → 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2S)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydrobenzofuran-4-carboxamide

HRID 2364690Notes

Reaction equation

HRID 2364690 reaction equation
[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:28][CH2:29][C@H:30]([OH:45])[CH2:31][N:32]5[CH2:37][CH2:36][N:35]([C:38](OC(C)(C)C)=O)[CH2:34][CH2:33]5)=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:46])[C:8](=[O:47])[C@H:7]2[CH2:48][CH3:49])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(=O)(O)[O-].[Na+].C1(C)C=CC(S(OC)(=O)=O)=CC=1>ClCCl.O1CCOCC1.O>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:28][CH2:29][C@H:30]([OH:45])[CH2:31][N:32]5[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]5)=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:46])[C:8](=[O:47])[C@H:7]2[CH2:48][CH3:49])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6645Methyl p-toluenesulfonateHCID 516892Sodium BicarbonateHCID 68107731tert-butyl 4-[(2S)-3-[[7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carbonyl]amino]-2-hydroxy-propyl]piperazine-1-carboxylate

Product 1

HCID 681076887-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2S)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydrobenzofuran-4-carboxamideYield 30%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Tert-butyl 4-[(2S)-3-[[7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carbonyl]amino]-2-hydroxy-propyl]piperazine-1-carboxylate 7d (580 mg, 0.85 mmol) was dissolved in 50 mL of dichloromethane followed by the addition of 20 mL of a 4 M solution of hydrogen chloride in dioxane. The reaction solution was stirred for 0.5 hours and concentrated under reduced pressure. The resulting residue was dissolved in 40 mL of acetonitrile followed by the addition of sodium bicarbonate (285 mg, 3.40 mmol) and methyl p-toluenesulfonate (316 mg, 1.70 mmol) and stirred for 12 hours. The resulting solution was added with 50 mL of water and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL×3), dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2S)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydrobenzofuran-4-carboxamide 8 (150 mg, yield: 30.0%) as a white solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in 40 mL of acetonitrile
  3. stirringstirred for 12 hours
  4. extractionextracted with dichloromethane (50 mL×3)
  5. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-89e4b63908144693b574ede3424ee415
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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