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

HRID 1947914Notes

Reaction equation

HRID 1947914 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:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][CH:14]=2)[N:3]=1.[NH2:28][C:29]1[CH:30]=[CH:31][C:32]([Br:40])=[C:33]2[C:37]=1[C:36](=[O:38])[N:35]([CH3:39])[CH2:34]2>>[CH2:20]([O:19][P:18]([CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:4]2[N:3]=[C:2]([NH:28][C:29]3[CH:30]=[CH:31][C:32]([Br:40])=[C:33]4[C:37]=3[C:36](=[O:38])[N:35]([CH3:39])[CH2:34]4)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[CH:14][CH:15]=1)(=[O:25])[O:22][CH2:23][CH3:24])[CH3:21]

Participants

3

Reactant 2

HCID 534084597-Amino-4-bromo-2-methylisoindolin-1-oneHCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 58292897Diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonateYield 38%

Procedure

The title compound was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (50.0 mg, 0.118 mmol) and 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (34.14 mg, 0.1416 mmol). The reaction mixture was concentrated under reduced pressure to yield a yellow oil which was purified on an ISCO Combiflash system using (DCM/MeOH 100:0→95:5) as eluent to isolate 28.1 mg of the title compound (38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.19 (t, J=7.07 Hz, 6H), 3.09 (s, 3H), 3.18-3.27 (m, 2H), 3.92-4.03 (m, 4H), 4.43 (s, 2H), 7.23-7.33 (m, 8H), 7.55 (br. s., 5H), 7.63 (d, J=8.84 Hz, 4H), 8.50 (s, 4H), 9.95 (s, 4H), 10.54 (br. s., 3H). MS (ES+): m/z 627.95/629.93 (91/100) [MH+]. HPLC: tR=3.72 min (ZQ3, polar—5 min).

Workup

  1. customThe title compound was prepared
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto yield a yellow oil which
  4. customwas purified on an ISCO Combiflash system

Sources & evidence

ORD record
ord-338e4329f51d45b3b17d81471cbd43b4
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

Loading…