Trifluoroacetic acid → Diethyl [4-({4-[(2-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxybenzyl]phosphonate trifluoroacetate

HRID 1947987Notes

Reaction equation

HRID 1947987 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)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=2)=[C:12]([O:28][CH3:29])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[NH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:39]=1[C:38](=[O:40])[N:37]([OH:41])[CH2:36]2.[C:42]([OH:48])([C:44]([F:47])([F:46])[F:45])=[O:43]>>[F:45][C:44]([F:47])([F:46])[C:42]([OH:48])=[O:43].[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]([NH:30][C:31]3[CH:32]=[CH:33][CH:34]=[C:35]4[C:39]=3[C:38](=[O:40])[N:37]([OH:41])[CH2:36]4)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=2)=[C:12]([O:28][CH3:29])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 672547907-Amino-2,3-dihydro-2-hydroxy-1H-isoindol-1-one2×HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Product 1

HCID 86654035Diethyl [4-({4-[(2-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxybenzyl]phosphonate trifluoroacetateYield 7%

Procedure

The title product was prepared according to the procedure for Example 102 using diethyl(4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (50.0 mg, 0.11 mmol) and 7-amino-2-hydroxy-2,3-dihydro-1H-isoindol-1-one (Compound 186A, 21.70 mg, 0.13 mmol). The reaction mixture purified by MDP to isolate the desired product (4.6 mg, yield: 7%) as a TFA salt. 1H NMR (CD3OD, 400 MHz): δ=1.29 (t, J=7.2 Hz, 6H), 3.33 (d, J=21.2 Hz, 2H), 3.89 (s, 3H), 4.06-4.13 (m, 4H), 4.63 (s, 2H), 4.96 (dt, J=2.8, 8.4 Hz, 1H), 7.10 (t, J=2.0 Hz, 1H), 7.24 (d, J=7.6 Hz, 1H), 7.36 (dd, J=0.8, 8.0 Hz, 0.5H), 7.52 (m, 1H), 7.66 (d, J=8.0 Hz, 1H), 8.32 (d, J=8.0 Hz, 0.5H), 8.37 (s, 1H). MS (ES+): m/z 582.17 [MH+]. HPLC: tR=3.64 min (OpenLynx, polar—5 min).

Workup

  1. customThe title product was prepared
  2. customThe reaction mixture purified by MDP

Sources & evidence

ORD record
ord-c864e246fe0c400e910505ec6ddf08b4
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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