8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one → Diethyl [4-({4-[(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

HRID 511330Notes

Reaction equation

HRID 511330 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][CH:32]=[C:33]2[C:38]=1[C:37](=[O:39])[N:36]([CH3:40])[CH2:35][CH2:34]2>>[CH3:40][N:36]1[CH2:35][CH2:34][C:33]2[C:38](=[C:29]([NH:28][C:2]3[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]4[CH:14]=[CH:15][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:26][CH:27]=4)[N:3]=3)[CH:30]=[CH:31][CH:32]=2)[C:37]1=[O:39]

Participants

3

Reactant 2

HCID 162026268-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one2×HCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 58292914Diethyl [4-({4-[(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

Procedure

The title product was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (52.9 mg, 0.125 mmol) and 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (Compound 132A, 25 mg, 0.14 mmol). The crude material 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, giving the title material as a white solid, 42.0 mg (59%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.55 (br s, 1H), 9.82 (br s, 1H), 8.44 (s, 1H), 8.56 (br s, 1H), 7.58 (d, J=7.8 Hz, 2H), 7.40 (t, J=8.0 Hz, 1H), 7.19 (dd, J=8.6, 2.3 Hz, 2H), 6.97 (d, J=7.3 Hz, 1H), 3.95 (qd, J=7.4, 7.2 Hz, 4H), 3.56 (t, J=6.7 Hz, 2H), 3.18 (d, J=21.2 Hz, 2H), 3.06 (s, 3H), 2.97 (t, J=6.6 Hz, 2H), 1.18 (t, J=7.1 Hz, 6H). MS (ES+): m/z 564.16 (100) [MH+]. HPLC: tR=3.50 min (ZQ3, polar—5 min).

Workup

  1. custompurified
  2. washeluting with 0-5% MeOH
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ef639feeaf5043c6b1f8865b5e81f093
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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