2-Bromoacetamide → HCID 71244765, compound

HRID 80777Notes

Reaction equation

HRID 80777 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][C@H:30]2[CH3:35])[C:12]2[CH2:18][N:17]([C:19]3[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=3[CH3:28])[CH2:16][CH2:15][C:13]=2[N:14]=1.Br[CH2:37][C:38]([NH2:40])=[O:39].CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([N:29]2[CH2:34][CH2:33][N:32]([CH2:37][C:38]([NH2:40])=[O:39])[CH2:31][C@H:30]2[CH3:35])[C:12]2[CH2:18][N:17]([C:19]3[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=3[CH3:28])[CH2:16][CH2:15][C:13]=2[N:14]=1

Participants

6

Reactant 3

HCID 696322-BromoacetamideHCID 81531DiisopropylethylamineHCID 71244697HCID 71244697, compound

Product 1

HCID 71244765HCID 71244765, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (R)-2-(2,5-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(2-methylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (43 mg, 0.053 mmol), 2-bromoacetamide (14.6 mg, 0.106 mmol) and DIEA (0.074 mL, 0.424 mmol) in DCM (2 mL) was stirred at rt for 16 h. The reaction was then diluted with EtOAc, and washed successively with sat aq NaHCO3, and brine. The organic layer was then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by HPLC(C18, 15-85% acetonitrile in H2O with 0.1% NH4OH) to provide (R)-2-(4-(2-(2,5-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)acetamide. 1H NMR (400 MHz, DMSO-d6, at 120° C.) δ ppm 7.58 (s, 1 H) 7.08-7.18 (m, 5 H) 6.99 (d, J=1.64 Hz, 1 H) 6.87 (dd, J=7.71, 1.64 Hz, 1 H) 4.01-4.09 (m, 1 H) 3.89-4.01 (m, 2 H) 3.48-3.58 (m, 1 H) 3.37-3.47 (m, 1 H) 2.97 (t, J=5.87 Hz, 2 H) 2.81-2.90 (m, 3 H) 2.78 (d, J=10.36 Hz, 1 H) 2.61 (dd, J=11.62, 1.77 Hz, 1 H) 2.47 (s, 3 H) 2.40 (dd, J=11.31, 3.35 Hz, 1 H) 2.23-2.34 (m, 4 H) 2.20 (s, 3 H) 1.28 (d, J=6.44 Hz, 3 H) 1.19 (dd, J=6.95, 1.52 Hz, 6 H); MS (ESI+) m/z 527.4 (M+H)+.

Workup

  1. washwashed successively with sat aq NaHCO3, and brine
  2. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by HPLC(C18, 15-85% acetonitrile in H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-710289025884485ea48c9f4cecba8106
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

Loading…