Ethyl bromoacetate → 2-[3-(1-Adamantyl)-4-benzyloxyphenyl]-5-(carbethoxymethylamino)pyrimidine

HRID 508655Notes

Reaction equation

HRID 508655 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:10]([C:22]34[CH2:31][CH:26]5[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]5)[CH2:23]3)[CH2:29]4)[CH:9]=2)=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>CC(C)=O>[C:22]12([C:10]3[CH:9]=[C:8]([C:5]4[N:6]=[CH:7][C:2]([NH:1][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:3][N:4]=4)[CH:13]=[CH:12][C:11]=3[O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:23][CH:24]3[CH2:30][CH:28]([CH2:27][CH:26]([CH2:25]3)[CH2:31]1)[CH2:29]2

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 532600875-Amino-2-[3-(1-adamantyl)-4-benzyloxyphenyl]pyrimidine

Product 1

HCID 532602482-[3-(1-Adamantyl)-4-benzyloxyphenyl]-5-(carbethoxymethylamino)pyrimidineYield 89%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a suspension of 5-amino-2-[3-(1-adamantyl)-4-benzyloxyphenyl]pyrimidine (49 mg, 0.12 mmol) and K2CO3 (69 mg, 0.50 mmol) in acetone (5 mL) was added ethyl bromoacetate (53 μl, 0.48 mmol). The mixture was heated at reflux under argon for 19 h and cooled to room temperature. After removal of acetone at reduced pressure, the residue was diluted with water (8 mL) and extracted with EtOAc (60 mL). The extract was washed (H2O and brine) and dried. After solvent removal at reduced pressure, the residue was chromatographed (14% EtOAc/hexane) to give 53 mg (89%) of 2-[3-(1-adamantyl)-4-benzyloxyphenyl]-5-(carbethoxymethylamino)pyrimidine as a pale-tan solid, mp 153-156° C. IR 3455, 2901, 1710, 1179 cm−1; 1H NMR (CDCl3) δ 1.33 (t, J=7.2 Hz, 3H, OCH2CH3), 1.75 (bs, 6H, AdCH2), 2.07 (bs, 3H, AdCH), 2.24 (m, 6H, AdCH2), 4.31 (q, J=7.2 Hz, 2H, OCH2CH3), 4.60 (m, 1H, NH), 4.73 (s, 2H, NHCH2CO), 5.20 (s, 2H, C6H5CH2), 7.03 (d, J=8.4 Hz, 1H, 5′-ArH), 7.32-7.55 (m, 5H, C6H5), 8.17 (dd, J=8.4 Hz, 2.1 Hz, 1H, 6′-ArH), 8.32 (d, J=2.1 Hz, 1H, 2′-ArH), 8.46 ppm (s, 2H, 4-ArH, 6-ArH). HRMS calcd C31H35N3O3 [M+H]+ 498.2757. found 498.2762.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under argon for 19 h
  3. customAfter removal of acetone at reduced pressure
  4. additionthe residue was diluted with water (8 mL)
  5. extractionextracted with EtOAc (60 mL)
  6. washThe extract was washed (H2O and brine)
  7. customdried
  8. customAfter solvent removal at reduced pressure
  9. customthe residue was chromatographed (14% EtOAc/hexane)

Sources & evidence

ORD record
ord-f6df03d07f164490ae387828e35e93f9
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

Loading…