Diisopropylethylamine → HCID 46864561, compound

HRID 69697Notes

Reaction equation

HRID 69697 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:44]=[CH:45][C:46]=1[N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1)[C:40]([NH:42][CH3:43])=[O:41]>C(#N)CC.CS(C)=O>[Cl:36][C:37]1[CH:38]=[C:39]([CH:44]=[CH:45][C:46]=1[N:47]1[CH2:48][CH2:49][N:50]([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)[CH2:51][CH2:52]1)[C:40]([NH:42][CH3:43])=[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 667770613-chloro-N-methyl-4-(piperazin-1-yl)benzamide hydrochloride

Product 1

HCID 46864561HCID 46864561, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 7854PropionitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of (S)-3-((S)-3-(hydroxymethyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazin-6(6aH)-one (111 mg, 0.476 mmol) in propiononitrile (1.2 mL) was added (cyanomethyl)trimethylphosphonium iodide (139 mg, 0.571 mmol) and DIEA (249 μl, 1.428 mmol) and finally 3-chloro-N-methyl-4-(piperazin-1-yl)benzamide hydrochloride (138 mg, 0.476 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 (64 mg, 29% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.52 (br. s., 1H), 8.43 (d, J=4.3 Hz, 1H), 7.87 (s, 1H), 7.76 (dd, J=8.3, 1.5 Hz, 1H), 7.66 (d, J=2.0 Hz, 1H), 7.54-7.74 (m, 1H), 7.19 (d, J=8.1 Hz, 1H), 6.99 (br. s., 1H), 4.52 (d, J=12.6 Hz, 1H), 3.85 (br. s., 1H), 3.44 (br. s., 2H), 2.92 (d, J=4.5 Hz, 4H), 2.75 (d, J=4.5 Hz, 4H), 2.52-2.69 (m, 3H), 1.99-2.09 (m, 1H), 1.85 (d, J=12.4 Hz, 1H), 1.64 (d, J=12.4 Hz, 1H), 1.32-1.58 (m, 3H). [M+H] calc'd for C24H29ClN6O2, 469; found, 469.

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-13e1c8c6d7de4e379e60539e90bb0230
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Reaction notes

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