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

HRID 1948062Notes

Reaction equation

HRID 1948062 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([Cl:23])[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[CH2:28]([O:30]P(CC1C=CC(N)=C(OCC)C=1)(=O)OCC)[CH3:29].ClC1N=C(Cl)C(C(F)(F)F)=CN=1>>[CH2:6]([O:5][P:4]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17]2[N:22]=[C:21]([Cl:23])[C:20]([C:24]([F:26])([F:25])[F:27])=[CH:19][N:18]=2)=[C:14]([O:30][CH2:28][CH3:29])[CH:15]=1)(=[O:8])[O:3][CH2:1][CH3:2])[CH3:7]

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, 6H), 3.28 (s, 1H), 3.23 (s, 1H), 1.41 (t, J=6.95 Hz, 3H), 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-c982fa96f18a4f84ae1ab11bb4cb36a2
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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