2,4-Dichloro-5-(trifluoromethyl)pyrimidine → Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-ethoxybenzyl)phosphonate

HRID 511494Notes

Reaction equation

HRID 511494 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][CH:14]=2)[N:3]=1.NC1C=CC(CP(=O)(OCC)[O:35][CH2:36][CH3:37])=CC=1OCC.ClC1N=C(Cl)C(C(F)(F)F)=CN=1>>[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:35][CH2:36][CH3:37])[N:3]=1

Participants

4

Reactant 3

HCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonateHCID 86654046Diethyl(4-amino-3-ethoxybenzyl)phosphonate

Product 1

HCID 86654045Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-ethoxybenzyl)phosphonate

Procedure

The title compound was prepared according to the procedure for diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate using diethyl (4-amino-3-ethoxybenzyl)phosphonate and 2,4-dichloro-5-trifluoromethylpyrimidine. The crude material was purified on an ISCO CombiFlash®Rf 4X Organic Purification System eluting with 1:1 EtOAc-DCM/MeOH (100:0→95:5)] affording a mixture of both regioisomers. The product was further purified by MDP to afford 514 mg (30%) of the desired regioisomer. 1H NMR (400 MHz, MeOD) δ 8.62 (s, 1H), 8.02 (d, J=8.08 Hz, 1H), 7.03 (t, J=2.15 Hz, 1H), 6.92 (td, J=2.34, 8.21 Hz, 1H), 4.04-4.22 (m, 6 H), 3.28 (s, 1H), 3.23 (s, 1H), 1.41 (t, J=6.95 Hz, 3 H), 1.27 (t, J=7.07 Hz, 7H). MS (ES+): m/z 468.07/470.09 (100/90) [MH+]. HPLC: tR=1.66 min (Micromass TOF: polar—3 min).

Workup

  1. customThe crude material was purified on an ISCO CombiFlash®Rf 4X Organic Purification System
  2. washeluting with 1:1 EtOAc-DCM/MeOH (100:0→95:5)]
  3. customaffording
  4. additiona mixture of both regioisomers
  5. customThe product was further purified by MDP
  6. customto afford 514 mg (30%) of the desired regioisomer
  7. customHPLC: tR=1.66 min (Micromass TOF: polar—3 min)

Sources & evidence

ORD record
ord-8633747d82d8480b972265ffd74aa373
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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