Diisopropylethylamine → HCID 58324391, compound

HRID 69696Notes

Reaction equation

HRID 69696 reaction equation
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][CH2:16][C@H:8]3[C:7](=[O:17])[NH:6][C:5]=2[CH:4]=1.[I-].C(C[P+](C)(C)C)#N.CCN(C(C)C)C(C)C.Cl.[Cl:36][C:37]1[CH:38]=[C:39]([CH:45]=[CH:46][C:47]=1[N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)[C:40]([NH:42][CH2:43][CH3:44])=[O:41]>C(#N)CC.CS(C)=O>[Cl:36][C:37]1[CH:38]=[C:39]([CH:45]=[CH:46][C:47]=1[N:48]1[CH2:49][CH2:50][N:51]([CH2:2][C:3]2[CH:12]=[N:11][C:10]3[N:9]4[CH2:13][CH2:14][CH2:15][CH2:16][C@H:8]4[C:7](=[O:17])[NH:6][C:5]=3[CH:4]=2)[CH2:52][CH2:53]1)[C:40]([NH:42][CH2:43][CH3:44])=[O:41]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 58324368(S)-3-(hydroxymethyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-6(6aH)-oneHCID 667760533-chloro-N-ethyl-4-(piperazin-1-yl)benzamide hydrochloride

Product 1

HCID 58324391HCID 58324391, compoundYield 41.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 7854PropionitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of (S)-3-(hydroxymethyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazin-6(6aH)-one (81 mg, 0.347 mmol) in propiononitrile (1.2 mL) was added (cyanomethyl)trimethylphosphonium iodide (101 mg, 0.417 mmol) and DIEA (182 μl, 1.042 mmol) and finally 3-chloro-N-ethyl-4-(piperazin-1-yl)benzamide hydrochloride (106 mg, 0.347 mmol). The vial was heated to 90° C. for 16 hours. The crude r×n was cooled to RT, DMSO (1 ml) was added, and purified via HPLC (55-90, basic). The fractions were collected, concentrated until a precipitate was visible and filtered. The solids were washed with water and collected to retrieve the product as a white solid (70 mg, 20% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.48 (s, 1H), 8.43 (t, J=5.4 Hz, 1H), 7.87 (d, J=2.3 Hz, 1H), 7.76 (dd, J=8.3, 2.0 Hz, 1H), 7.66 (d, J=1.8 Hz, 1H), 7.17 (d, J=8.6 Hz, 1H), 6.97 (d, J=2.0 Hz, 1H), 4.50 (d, J=12.9 Hz, 1H), 3.84 (dd, J=11.4, 2.8 Hz, 1H), 3.38 (s, 2H), 3.18-3.31 (m, 2H), 3.03 (br. s., 4H), 2.60 (td, J=12.7, 2.7 Hz, 1H), 2.51 (br. s., 4H), 2.04 (d, J=12.9 Hz, 1H), 1.85 (d, J=12.1 Hz, 1H), 1.64 (d, J=12.6 Hz, 1H), 1.32-1.58 (m, 3H), 1.10 (t, J=7.1 Hz, 3H). [M+H] calc'd for C25H31ClN6O2, 483; found, 483.

Workup

  1. temperatureThe crude r×n was cooled to RT
  2. custompurified via HPLC (55-90, basic)
  3. customThe fractions were collected
  4. concentrationconcentrated until a precipitate
  5. filtrationfiltered
  6. washThe solids were washed with water
  7. customcollected

Sources & evidence

ORD record
ord-91342ebceff14da397a56381213c5a0d
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Reaction notes

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