Ammonia → 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

HRID 2364688Notes

Reaction equation

HRID 2364688 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:18])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.[CH:19]1([N:24]2[C:33]3[N:32]=[C:31]([NH:34][C:35]4[CH:36]=[CH:37][C:38]([C:44](O)=[O:45])=[C:39]5[C:43]=4[O:42][CH2:41][CH2:40]5)[N:30]=[CH:29][C:28]=3[N:27]([CH3:47])[C:26](=[O:48])[C@H:25]2[CH2:49][CH3:50])[CH2:23][CH2:22][CH2:21][CH2:20]1.C(N(C(C)C)CC)(C)C.N>ClCCl.O>[CH:19]1([N:24]2[C:33]3[N:32]=[C:31]([NH:34][C:35]4[CH:36]=[CH:37][C:38]([C:44]([NH:1][CH2:2][C@H:3]([OH:18])[CH2:4][N:5]5[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH2:7][CH2:6]5)=[O:45])=[C:39]5[C:43]=4[O:42][CH2:41][CH2:40]5)[N:30]=[CH:29][C:28]=3[N:27]([CH3:47])[C:26](=[O:48])[C@H:25]2[CH2:49][CH3:50])[CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 7144880tert-butyl 4-[(2S)-3-amino-2-hydroxy-propyl]piperazine-1-carboxylateHCID 681074757-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

Product 1

HCID 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-carboxylateYield 32.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-[(2S)-3-amino-2-hydroxy-propyl]piperazine-1-carboxylate 7c (355 mg, 1.37 mmol), 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (600 mg, 1.37 mmol), O-(benzotriazol-1-yl)-N,N,N′-tetra methyluronium tetrafluoroborate (440 mg, 1.37 mmol) and diisopropylethylamine (390 mg, 3.01 mmol) were dissolved in 40 mL of dichloromethane. The reaction solution was stirred for 2 hours. The resulting solution was added with 50 mL of water and 10 mL of aqueous ammonia successively, stirred for 0.5 hours, extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL), 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 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 (300 mg, yield: 32.3%) as a white solid.

Workup

  1. stirringstirred for 0.5 hours
  2. extractionextracted with dichloromethane (50 mL×3)
  3. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9fc849e0516044f09f005798114cccb6
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

Loading…