2,4-Dichloro-5-(trifluoromethyl)pyrimidine → Diethyl [(5-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-6-methoxypyridin-2-yl)methyl]phosphonate

HRID 1948095Notes

Reaction equation

HRID 1948095 reaction equation
ClC1C(C(F)(F)F)=CN=C(NC2C=CC(CP(=O)(OCC)OCC)=CC=2)N=1.Cl[C:29]1[N:34]=[C:33]([Cl:35])[C:32]([C:36]([F:39])([F:38])[F:37])=[CH:31][N:30]=1.[CH2:40]([O:42][P:43]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([NH2:55])=[C:51]([O:56][CH3:57])[N:50]=1)(=[O:47])[O:44][CH2:45][CH3:46])[CH3:41]>>[CH2:40]([O:42][P:43]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([NH:55][C:29]2[N:34]=[C:33]([Cl:35])[C:32]([C:36]([F:39])([F:38])[F:37])=[CH:31][N:30]=2)=[C:51]([O:56][CH3:57])[N:50]=1)(=[O:47])[O:44][CH2:45][CH3:46])[CH3:41]

Participants

4

Reactant 3

HCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonateHCID 86654056Diethyl[(5-amino-6-methoxypyridin-2-yl)methyl]phosphonate2×

Product 1

HCID 86654055Diethyl [(5-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-6-methoxypyridin-2-yl)methyl]phosphonateYield 61%

Procedure

The title compound was prepared according to the procedure for diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate using 2,4-dichloro-5-trifluoromethylpyrimidine and diethyl[(5-amino-6-methoxypyridin-2-yl)methyl]phosphonate (Compound 286B). The crude material was purified by column chromatography (methylene chloride:CH3CN=0-20%) to obtain a mixture of 2 regioisomers with a ratio of roughly 4:1 (the major one is the desired title compound [364 mg, 61% yield]). 1H NMR (400 MHz, DMSO-d6) δ=1.22 (t, J=6.9 Hz, 6H), 3.35 (d, J=21.7 Hz, 2H), 3.87 (s, 3H), 4.00-4.07 (m, 4H), 6.98 (dd, J=7.8, 2.8 Hz, 1H), 7.83 (d, J=7.6 Hz, 1H), 8.72 (s, 1H), 9.90 (s, 1H). MS (ES+): m/z 455.21 (100), 457.15 (33) [MH+]; HPLC: tR=1.41 min (UPLC, Analytical).

Workup

  1. customThe title compound was prepared
  2. customThe crude material was purified by column chromatography (methylene chloride:CH3CN=0-20%)
  3. customto obtain
  4. additiona mixture of 2 regioisomers with a ratio of roughly 4:1 (the major one

Sources & evidence

ORD record
ord-69195cd47afc4bb9a7f4ffb791a901c9
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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