Sodium Carbonate → ethyl(E)-3-[2-(3-(1-adamantyl)-4-benzyloxyphenyl)-5-pyrimidinyl]-2-propenoate

HRID 508652Notes

Reaction equation

HRID 508652 reaction equation
[C:1]12([C:11]3[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][C:16]=3[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.Cl[C:29]1[N:34]=[CH:33][C:32](/[CH:35]=[CH:36]/[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.C(OCC)(=O)C>[C:1]12([C:11]3[CH:12]=[C:13]([C:29]4[N:30]=[CH:31][C:32](/[CH:35]=[CH:36]/[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:33][N:34]=4)[CH:14]=[CH:15][C:16]=3[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 12134904[3-(Adamantan-1-yl)-4-(benzyloxy)phenyl]boronic acidHCID 53259409Ethyl (E)-3-(2-chloropyrimidin-5-yl)acrylate

Product 1

HCID 53258792ethyl(E)-3-[2-(3-(1-adamantyl)-4-benzyloxyphenyl)-5-pyrimidinyl]-2-propenoateYield 96.9%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(1-adamantyl)-4-benzyloxyphenylboronic acid (Zhang Y. et al., Blood, 2002; 100:2917-2925, Dawson M. I. et al., J. Med. Chem., 2004; 47:3518-3536) (3.62 g, 10.0 mmol) and ethyl (2E)-3-(2-chloro-5-pyrimidinyl)-2-propenoate (1.76 g, 8.30 mmol) in dimethoxyethane (50 mL) was added under argon tetrakis(triphenylphosphine)-palladium (1.15 g, 1.00 mmol) and 2 M aqueous Na2CO3 (10 mL). The reaction mixture was heated at reflux for 18 h, cooled to room temperature, diluted with ethyl acetate, washed (water and brine) and dried. After solvent removal at reduced pressure, the residue was chromatographed (9% to 14% ethyl acetate/hexane) to give 3.98 g (96%) of ethyl(E)-3-[2-(3-(1-adamantyl)-4-benzyloxyphenyl)-5-pyrimidinyl]-2-propenoate as a yellow solid, mp 164-167° C. IR 2903, 1710, 1432, 1225 cm−1; 1H NMR δ (CDCl3) 1.40 (t, J=7.2 Hz, 3H, OCH2CH3), 1.77 (bs, 6H, AdCH2), 2.11 (bs, 3H, AdCH), 2.26 (bs, 6H, AdCH2), 4.33 (q, J=7.2 Hz, 2H, OCH2CH3), 5.24 (s, 2H, CH2), 6.59 (d, J=16.2 Hz, 1H, CH═CHCO), 7.08 (d, J=8.7 Hz, 1H, 5-ArH), 7.35-7.58 (m, 5H, C6H5), 7.65 (d, J=16.2 Hz, 1H, CH═CHCO), 8.33 (dd, J=8.7 Hz, 2.1 Hz, 1H, 6-ArH), 8.47 (d, J=2.1 Hz, 1H, 2-ArH), 8.91 ppm (s, 2H, 4-PyrH, 6-PyrH). HRMS calcd C32H34N2O3 [M+H]+ 495.2642. found 495.2636.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. washwashed (water and brine)
  4. customdried
  5. customAfter solvent removal at reduced pressure
  6. customthe residue was chromatographed (9% to 14% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2b0f0a40a80343e7aef1767921d34f3f
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

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