Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-ethoxybenzyl)phosphonate → HCID 178466846, compound

HRID 511493Notes

Reaction equation

HRID 511493 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][C:14]=2[O:28][CH2:29][CH3:30])[N:3]=1.[NH2:31][C:32]1[CH:33]=[CH:34][C:35]([C@@H:43]2[CH2:48][CH2:47][C@H:46]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:45][CH2:44]2)=[C:36]2[C:40]=1[C:39](=[O:41])[N:38]([CH3:42])[CH2:37]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:31][C:32]3[CH:33]=[CH:34][C:35]([C@@H:43]4[CH2:44][CH2:45][C@H:46]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:47][CH2:48]4)=[C:36]4[C:40]=3[C:39](=[O:41])[N:38]([CH3:42])[CH2:37]4)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[C:14]([O:28][CH2:29][CH3:30])[CH:15]=1)([O:22][CH2:23][CH3:24])=[O:25])[CH3:21]

Participants

3

Reactant 2

HCID 86654045Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-ethoxybenzyl)phosphonate2×HCID 178472341HCID 178472341, compound

Product 1

HCID 178466846HCID 178466846, compoundYield 73.7%

Procedure

The title compound was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-ethoxybenzyl)phosphonate (Compound 244A 123.2 mg, 0.26 mmol) and ethyl cis-4-(7-amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohexanecarboxylate (100.0 mg, 0.32 mmol). The reaction mixture was concentrated in vacuo and purified by on an ISCO CombiFlash®Rf System eluting with: 0→5% MeOH in DCM] to afford 143.3 mg (73%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 8.44 (d, J=10.36 Hz, 1 H), 8.35 (s, 1 H), 7.89 (d, J=8.34 Hz, 1 H), 7.24 (d, J=8.59 Hz, 1 H), 7.06 (t, J=2.15 Hz, 1 H), 6.92 (dt, J=8.21, 2.21 Hz, 1 H), 4.52 (s, 2 H), 4.26 (q, J=7.16 Hz, 2 H), 4.05-4.19 (m, 6 H), 3.29 (s, 2 H), 3.19 (s, 3 H), 2.79 (br. s., 1 H), 2.63-2.73 (m, 1 H), 2.30 (d, J=7.33 Hz, 2 H), 1.76 (d, J=6.06 Hz, 6 H), 1.42 (t, J=6.95 Hz, 3 H), 1.27-1.38 (m, 9 H). MS (ES+): m/z 749.30/750.31 (100/25) [MH+]. HPLC: tR=1.82 min (Micromass TOF: polar—3 min).

Workup

  1. customThe title compound was prepared
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompurified by on an ISCO CombiFlash®Rf System
  4. washeluting with: 0→5% MeOH in DCM]

Sources & evidence

ORD record
ord-e19b2c894abc4dca948043a05f9ff805
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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