Trifluoroacetic acid → HCID 71244797, compound

HRID 80790Notes

Reaction equation

HRID 80790 reaction equation
[C:1](O)([C:3](F)(F)F)=[O:2].OC(C(F)(F)F)=O.[CH3:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[C:17]=1[C:23]1[N:24]=[C:25]([N:43]2[CH2:48][C@@H:47]([CH3:49])[NH:46][CH2:45][C@@H:44]2[CH3:50])[C:26]2[CH2:32][N:31]([C:33]3[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:36]=[CH:35][C:34]=3[CH3:42])[CH2:30][CH2:29][C:27]=2[N:28]=1.CCN(C(C)C)C(C)C.CC(OC(C)=O)=O>CCOC(C)=O.C(Cl)Cl>[CH3:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH3:15])[C:17]=1[C:23]1[N:24]=[C:25]([N:43]2[C@H:44]([CH3:50])[CH2:45][N:46]([C:1](=[O:2])[CH3:3])[C@@H:47]([CH3:49])[CH2:48]2)[C:26]2[CH2:32][N:31]([C:33]3[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:36]=[CH:35][C:34]=3[CH3:42])[CH2:30][CH2:29][C:27]=2[N:28]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 131731889HCID 131731889, compound

Product 1

HCID 71244797HCID 71244797, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the TFA salt of 2-(2,6-dimethylphenyl)-4-((trans)-2,5-dimethylpiperazin-1-yl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine TFA salt (0.113 g, 0.233 mmol), DIEA (0.33 mL, 1.87 mmol) and DCM (5 mL) was added Ac2O (0.044 mL, 0.467 mmol). The reaction was stirred at rt for 1 h before being diluted with EtOAc. The solution was washed with sat aq NaHCO3 and then brine before the organic layers were separated and then dried (Na2SO4), filtered and concentrated. The residue was then purified by FCC (35-45% EtOAc/heptane) to give racemic-1-(4-(2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-(trans)-2,5-dimethylpiperazin-1-yl)ethanone. 1H NMR (400 MHz, DMSO-d6, at 100° C.) δ ppm 7.14-7.19 (m, 1 H) 7.05-7.12 (m, 3 H) 6.91 (d, J=1.39 Hz, 1 H) 6.86 (dd, J=7.71, 1.52 Hz, 1 H) 4.29 (dt, J=6.22, 3.27 Hz, 1 H) 4.12-4.18 (m, 1 H) 4.00-4.07 (m, 1 H) 3.50-3.58 (m, 1 H) 3.41-3.47 (m, 1 H) 3.39 (t, J=6.19 Hz, 2 H) 2.93 (br. s., 4 H) 2.84 (dt, J=13.80, 6.93 Hz, 1 H) 2.52 (br. s., 1 H) 2.25 (s, 3 H) 2.08 (s, 6 H) 2.01 (s, 3 H) 1.19 (dd, J=6.95, 2.40 Hz, 6 H) 1.10-1.17 (m, 6 H); MS (ESI+) m/z 526.4 (M+H)+.

Workup

  1. washThe solution was washed with sat aq NaHCO3
  2. custombrine before the organic layers were separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was then purified by FCC (35-45% EtOAc/heptane)

Sources & evidence

ORD record
ord-8b0fbf8803fc43379d64298509c1e792
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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