HCID 67254174, compound → HCID 58292966, compound

HRID 511316Notes

Reaction equation

HRID 511316 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:41])=[C:33]2[C:38]=1[C:37](=[O:39])[N:36]([CH3:40])[CH:35]=[CH:34]2>>[Br:41][C:32]1[CH:31]=[CH:30][C:29]([NH:28][C:2]2[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[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]=3)[N:3]=2)=[C:38]2[C:33]=1[CH:34]=[CH:35][N:36]([CH3:40])[C:37]2=[O:39]

Participants

3

Reactant 2

HCID 67254174HCID 67254174, compound2×HCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 58292966HCID 58292966, compoundYield 62.8%

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 (166.9 mg, 0.3939 mmol) and 8-amino-5-bromo-2-methylisoquinolin-1(2H)-one (Compound 123A, 120 mg, 0.47 mmol). The crude material was adsorbed onto a pre-filled silica gel loading cartridge and purified using an ISCO Combiflash system eluting first with 0-100% EtOAc:CH2Cl2 and then 15% MeOH:EtOAc. The desired fractions were pooled together and concentrated in vacuo. The material was further purified by trituration in CH2Cl2 and heptane to afford the title product (158.3 mg 62%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.28 (br s, 1H), 9.90 (s, 1H), 8.82 (br s, 1H), 8.50 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.70 (d, J=7.6 Hz, 1H), 7.58 (br d, J=5.6 Hz, 2H), 7.25 (dd, J=8.6, 2.3 Hz, 2H), 6.82 (d, J=7.6 Hz, 1H), 3.90-4.03 (m, 4H), 3.55 (s, 3H), 3.21 (d, J=21.2 Hz, 2H), 1.19 (t, J=6.9 Hz, 6H). MS (ES+): m/z 640.03/642.05 (96/100) [MH+]. HPLC: tR=3.90 min (ZQ3, polar—5 min).

Workup

  1. customThe title compound was prepared
  2. custompurified
  3. washeluting first with 0-100% EtOAc
  4. concentrationconcentrated in vacuo
  5. customThe material was further purified by trituration in CH2Cl2

Sources & evidence

ORD record
ord-695369564f0b431ba3dcdf12a1acecb3
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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