5-Aminovaleric acid → 5-(2-Chloro-6-morpholinopyrimidin-4-ylamino)pentanoic acid

HRID 1043814Notes

Reaction equation

HRID 1043814 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7].[Cl:9][C:10]1[N:15]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH:13]=[C:12](Cl)[N:11]=1.CCN(C(C)C)C(C)C>CN(C)C=O.CCOC(C)=O>[Cl:9][C:10]1[N:11]=[C:12]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7])[CH:13]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:15]=1

Participants

6

Reactant 3

HCID 1385-Aminovaleric acidHCID 81531DiisopropylethylamineHCID 115866994-(2,6-Dichloropyrimidin-4-yl)morpholine

Product 1

HCID 866458885-(2-Chloro-6-morpholinopyrimidin-4-ylamino)pentanoic acidYield 60.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

5-Aminopentanoic acid (140 mg, 1.19 mmol), 4-(2,6-dichloropyrimidin-4-yl)morpholine (prepared as in Method 22; 234 mg, 1.0 mmol) and DIEA (0.530 mL, 3.0 mmol) were dissolved in N,N-dimethylformamide (6 mL). The reaction solution was stirred at 40° C. for 40 hours. The reaction was diluted with EtOAc (100 mL) and washed with 0.5 M HCl (40 mL), water (40 mL), brine (40 mL), dried with Na2SO4, filtered and evaporated to give a solid. The crude product was chromatographed on a silica gel column by eluting with 80% EtOAc in hexane to give 5-(2-chloro-6-morpholinopyrimidin-4-ylamino)pentanoic acid as a white solid (190 mg, 60%). LC/MS (m/z): 315.0 (MH+), Rf 1.79 minutes.

Workup

  1. washwashed with 0.5 M HCl (40 mL), water (40 mL), brine (40 mL)
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customto give a solid
  6. customThe crude product was chromatographed on a silica gel column
  7. washby eluting with 80% EtOAc in hexane

Sources & evidence

ORD record
ord-191932da8ae44fa6aca863bbbc8bdf7e
Source dataset
uspto-grants-2013_10
Patent number
US08563549B2

Reaction notes

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