Diisopropylethylamine → HCID 59224689, compound

HRID 1811724Notes

Reaction equation

HRID 1811724 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([S:8][CH2:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[C:4]([Cl:14])[N:3]=1.O.ON1C2C=CC=CC=2N=N1.[CH3:26][O:27][C:28](=[O:42])[C@@H:29]([NH2:41])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O.O>[CH3:26][O:27][C:28](=[O:42])[C@@H:29]([NH:41][C:11](=[O:13])[CH2:10][CH2:9][S:8][C:6]1[CH:5]=[C:4]([Cl:14])[N:3]=[C:2]([NH2:1])[N:7]=1)[CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:38])([CH3:40])[CH3:39])=[O:35]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7019762HCID 7019762, compoundHCID 59224706HCID 59224706, compound

Product 1

HCID 59224689HCID 59224689, compoundYield 94.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

3-(2-Amino-6-chloropyrimidin-4-ylsulfanyl)propionic acid (211 mg, 0.903 mmol) obtained in Step 1 of Example 2-8 was dissolved in a mixture of dichloromethane (5.0 ml) and N,N-dimethylformamide (2.0 ml), and then 1-hydroxybenzotriazole monohydrate (139 mg, 0.887 mmol), (S)-2-amino-5-tert-butoxycarbonylaminopentanoic acid methyl ester (202 mg, 0.822 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (173 mg, 0.902 mmol), and diisopropylethylamine (0.157 ml, 0.901 mmol) were added thereto. After the resulting mixture was stirred at room temperature for four hours, water (30 ml) was added to the reaction solution. The mixture was extracted three times with ethyl acetate (30 ml). The organic layers were combined together and then sequentially washed with a saturated aqueous sodium chloride solution (20 ml), a saturated aqueous sodium bicarbonate solution (20 ml), and a saturated aqueous sodium chloride solution (20 ml). The washed organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1) to yield (S)-2-[3-(2-amino-6-chloropyrimidin-4-ylsulfanyl)propionylamino]-5-tert-butoxycarbonylamino pentanoic acid methyl ester (359 mg) as a white amorphous material.

Workup

  1. extractionThe mixture was extracted three times with ethyl acetate (30 ml)
  2. washsequentially washed with a saturated aqueous sodium chloride solution (20 ml)
  3. dry with materialThe washed organic layer was dried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1)

Sources & evidence

ORD record
ord-8720158c41a34008865fdbe0bcf7ffc2
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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