2-amino-5-(4-hydroxycyclohexyl)-N,N-dimethylbenzamide → HCID 178476869, compound

HRID 1947998Notes

Reaction equation

HRID 1947998 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][CH3:29])[N:3]=1.[NH2:30][C:31]1[CH:41]=[CH:40][C:39]([CH:42]2[CH2:47][CH2:46][CH:45]([OH:48])[CH2:44][CH2:43]2)=[CH:38][C:32]=1[C:33]([N:35]([CH3:37])[CH3:36])=[O:34]>>[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:30][C:31]3[CH:41]=[CH:40][C:39]([C@H:42]4[CH2:43][CH2:44][C@H:45]([OH:48])[CH2:46][CH2:47]4)=[CH:38][C:32]=3[C:33](=[O:34])[N:35]([CH3:36])[CH3:37])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[C:14]([O:28][CH3:29])[CH:15]=1)(=[O:25])[O:22][CH2:23][CH3:24])[CH3:21]

Participants

3

Reactant 2

HCID 672547852-amino-5-(4-hydroxycyclohexyl)-N,N-dimethylbenzamide2×HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Product 1

HCID 178476869HCID 178476869, compound

Procedure

The title compounds were prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (0.20 g, 0.45 mmol) and 2-amino-5-(4-hydroxycyclohexyl)-N,N-dimethylbenzamide (Compound 173A, 0.130 g, 0.496 mmol). The reaction mixture was partitioned between EtOAc and water and separated. The aqueous was extracted with EtOAc (3×) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated. The compound was purified on an Isco Combiflash unit eluting with 0 to 5% MeOH in DCM to afford the individual trans and cis isomers. Cis: 1H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.43 (s, 1H), 8.32 (s, 1H), 7.86 (d, J=8.34 Hz, 1H), 7.60 (d, J=7.83 Hz, 1H), 7.26 (dd, J=1.77, 8.59 Hz, 1H), 7.22 (d, J=2.02 Hz, 1H), 6.96 (t, J=1.89 Hz, 1H), 6.73 (d, J=7.83 Hz, 1H), 3.92-4.01 (m, 4H), 3.89 (br. s., 1H), 3.77 (s, 3H), 3.13-3.23 (m, 2H), 2.91 (d, J=15.16 Hz, 6H), 2.56 (t, J=11.87 Hz, 1H), 1.79-1.92 (m, 2H), 1.70-1.78 (m, 2H), 1.49-1.61 (m, 4H), 1.18 (t, J=7.07 Hz, 6H); MS (ES+): m/z: 681.2723 [MH+]. HPLC: tR=1.45 min (UPLC TOF MS: polar—3 min). Trans: 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.44 (s, 1H), 8.32 (s, 1H), 7.85 (d, J=8.84 Hz, 1H), 7.58 (d, J=8.08 Hz, 1H), 7.26 (dd, J=2.02, 8.34 Hz, 1H), 7.22 (d, J=2.02 Hz, 1H), 6.96 (s, 1H), 6.73 (d, J=7.83 Hz, 1H), 4.57 (d, J=4.55 Hz, 1H), 3.91-4.01 (m, 4H), 3.76 (s, 3H), 3.40-3.54 (m, 1H), 3.14-3.23 (m, 2H), 2.91 (d, J=18.95 Hz, 6H), 1.93 (d, J=9.35 Hz, 2H), 1.79 (d, J=12.38 Hz, 2H), 1.45-1.58 (m, 2H), 1.22-1.35 (m, 2H), 1.19 (t, J=7.07 Hz, 6H); MS (ES+): m/z: 680.2332 [MH+]. HPLC: tR=1.40 min (UPLC TOF MS: polar—3 min).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. customseparated
  3. extractionThe aqueous was extracted with EtOAc (3×)
  4. washthe combined organic fractions were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe compound was purified on an Isco Combiflash unit
  9. washeluting with 0 to 5% MeOH in DCM
  10. customto afford the individual trans and cis isomers
  11. customHPLC: tR=1.45 min (UPLC TOF MS: polar—3 min)
  12. customHPLC: tR=1.40 min (UPLC TOF MS: polar—3 min)

Sources & evidence

ORD record
ord-9b68188965d147418ca5eb16a0521fbd
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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