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

HRID 511526Notes

Reaction equation

HRID 511526 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.[NH2:40][C:41]1[CH:42]=[CH:43][C:44]([CH2:49][P:50](=[O:57])([O:54][CH2:55][CH3:56])[O:51][CH2:52][CH3:53])=[N:45][C:46]=1[O:47][CH3:48]>>[Cl:35][C:33]1[C:32]([C:36]([F:39])([F:38])[F:37])=[CH:31][N:30]=[C:29]([NH:40][C:41]2[CH:42]=[CH:43][C:44]([CH2:49][P:50](=[O:57])([O:54][CH2:55][CH3:56])[O:51][CH2:52][CH3:53])=[N:45][C:46]=2[O:47][CH3:48])[N:34]=1

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, 6 H), 3.35 (d, J=21.7 Hz, 2 H), 3.87 (s, 3 H), 4.00-4.07 (m, 4 H), 6.98 (dd, J=7.8, 2.8 Hz, 1 H), 7.83 (d, J=7.6 Hz, 1 H), 8.72 (s, 1 H), 9.90 (s, 1 H). 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-ec0805d72c5f4d17a41f854c04720508
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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