7-Amino-2-methyl-2,3-dihydro-1H-isoindol-1-one → Bis(2,2,2-trifluoroethyl) [3-methoxy-4-({4-[(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino) benzyl]phosphonate

HRID 511319Notes

Reaction equation

HRID 511319 reaction equation
Cl[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:33]=[CH:32][C:16]([CH2:17][P:18](=[O:31])([O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:15][C:14]=2[O:34][CH3:35])[N:3]=1.[NH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[C:41]2[C:45]=1[C:44](=[O:46])[N:43]([CH3:47])[CH2:42]2>>[CH3:35][O:34][C:14]1[CH:15]=[C:16]([CH:32]=[CH:33][C:13]=1[NH:12][C:4]1[N:3]=[C:2]([NH:36][C:37]2[CH:38]=[CH:39][CH:40]=[C:41]3[C:45]=2[C:44](=[O:46])[N:43]([CH3:47])[CH2:42]3)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=1)[CH2:17][P:18](=[O:31])([O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[O:19][CH2:20][C:21]([F:24])([F:23])[F:22]

Participants

3

Reactant 2

HCID 450887127-Amino-2-methyl-2,3-dihydro-1H-isoindol-1-oneHCID 86654019Bis(2,2,2-trifluoroethyl) (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 58292948Bis(2,2,2-trifluoroethyl) [3-methoxy-4-({4-[(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino) benzyl]phosphonate

Procedure

The title compound was prepared according to the procedure for Example 102 using bis(2,2,2-trifluoroethyl) (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 124A, 67.0 mg, 0.119 mmol) and 7-amino-2-methyl-2,3-dihydro-1H-isoindol-1-one (Preparation XXXVIII, 26.9 mg, 0.166 mmol). The crude product was adsorbed onto a pre-filled solid loading cartridge and purified using the Teledyne/ISCO Combiflash system eluting with 0-5% MeOH:CH2Cl2. The desired fractions were pooled together and concentrated in vacuo. The material was further purified by MDP (under basic conditions; ammonium bicarbonate buffer, pH 9), which afforded the title material as an off-white solid, 54.8 mg (64%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.60 (s, 1H), 9.13 (s, 1H), 8.40 (s, 1H), 8.37 (br s, 1H), 7.49 (br d, J=7.1 Hz, 1H), 7.37 (br t, J=7.1 Hz, 1H), 7.15 (d, J=7.6 Hz, 1H), 7.06 (s, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.60-4.74 (m, 4H), 4.45 (s, 2H), 3.74 (s, 3H), 3.61 (d, J=22.2 Hz, 2H), 3.06 (s, 3H). MS (ES+): m/z 688.08 (100) [MH+]. HPLC: tR=3.72 min (ZQ3, polar—5 min).

Workup

  1. custompurified
  2. washeluting with 0-5% MeOH
  3. concentrationconcentrated in vacuo
  4. customThe material was further purified by MDP (under basic conditions; ammonium bicarbonate buffer, pH 9), which

Sources & evidence

ORD record
ord-7b1ccb1053ad4d3796d7be50f4d0514c
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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