Propylamine → HCID 90402669, compound

HRID 2200735Notes

Reaction equation

HRID 2200735 reaction equation
[Cl:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][C:18](O)=[O:19])[C:12](=[O:21])[N:11]([CH3:22])[C:10]=3[N:9]=[C:8]2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:33])[F:32])[CH:25]=2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:49]([NH2:52])[CH2:50][CH3:51]>CN(C=O)C.O>[Cl:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][C:18]([NH:52][CH2:49][CH2:50][CH3:51])=[O:19])[C:12](=[O:21])[N:11]([CH3:22])[C:10]=3[N:9]=[C:8]2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:33])([F:34])[F:32])[CH:25]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 7852PropylamineHCID 682631,1'-CarbonyldiimidazoleHCID 90402760HCID 90402760, compound

Product 1

HCID 90402669HCID 90402669, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(7-(4-Chlorobenzyl)-3-methyl-2,6-dioxo-8-(3-(trifluoromethoxy)phenoxy)-2,3,6,7-tetrahydro-1H-purin-1-yl)acetic acid (0.25 g, 0.48 mmol, Example 361) and CDI (0.93 g, 0.57 mmol) were combined in DMF (4 mL) and stirred at room temperature for 20 min. Propan-1-amine was added and the reaction was stirred at room temperature for 3 h. The reaction was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were washed with 1N lithium chloride (2×75 mL), dried with magnesium sulfate, filtered and evaporated under reduced pressure to a white solid. Solid was purified using a 25 g silica gel flash column eluted with 1% methanol/DCM to give 2-(7-(4-chlorobenzyl)-3-methyl-2,6-dioxo-8-(3-(trifluoromethoxy)phenoxy)-2,3,6,7-tetrahydro-1H-purin-1-yl)-N-propylacetamide (0.13 g, 47% yield) as a white solid. LCMS retention time=4.070 min and 99% purity, LCMS MH+ 566. 1H NMR (DMSO-d6) δ 7.99 (t, NH), 7.60 (t, 1H, J=8 Hz), 7.48-7.52 (m, 1H), 7.39-7.46 (m, 5H), 7.32 (d, 1H, J=8 Hz), 5.42 (s, 2H), 4.42 (s, 2H), 3.31 (s, 3H), 3.00 (dd, 2H, J=8 Hz and 16 Hz), 1.34-1.45 (m, 2H), 0.83 (t, 3H, J=8 Hz).

Workup

  1. stirringthe reaction was stirred at room temperature for 3 h
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. washThe combined extracts were washed with 1N lithium chloride (2×75 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure to a white solid
  7. customSolid was purified
  8. washeluted with 1% methanol/DCM

Sources & evidence

ORD record
ord-ff86e83d30e943729e293fad7c3d42f7
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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