Diisopropylethylamine → HCID 46864562, compound

HRID 69699Notes

Reaction equation

HRID 69699 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.Cl.[F:27][C:28]1[CH:29]=[C:30]([CH:35]=[CH:36][C:37]=1[N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)[C:31]([NH:33][CH3:34])=[O:32].CCN(C(C)C)C(C)C>C(#N)CC.CS(C)=O>[F:27][C:28]1[CH:29]=[C:30]([CH:35]=[CH:36][C:37]=1[N:38]1[CH2:39][CH2:40][N:41]([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)[CH2:42][CH2:43]1)[C:31]([NH:33][CH3:34])=[O:32]

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 66775588HCID 66775588, compound

Product 1

HCID 46864562HCID 46864562, compoundYield 33.2%

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 (129 mg, 0.553 mmol) in propiononitrile (1.2 mL) was added ((cyanomethyl)trimethylphosphonium iodide (161 mg, 0.664 mmol)) and 3-fluoro-N-methyl-4-(piperazin-1-yl)benzamide hydrochloride (151 mg, 0.553 mmol) and DIEA (290 μl, 1.659 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 (83 mg, 33% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.48 (s, 1H), 8.33 (d, J=4.5 Hz, 1H), 7.45-7.70 (m, 3H), 6.88-7.10 (m, 2H), 4.50 (d, J=12.9 Hz, 1H), 3.83 (dd, J=11.1, 2.5 Hz, 1H), 3.36 (s, 2H), 3.08 (br. s., 4H), 2.75 (d, J=4.5 Hz, 3H), 2.56-2.64 (m, 1H), 2.50 (br. s., 4H), 1.97-2.12 (m, 1H), 1.85 (d, J=11.1 Hz, 1H), 1.63 (d, J=11.9 Hz, 1H), 1.29-1.57 (m, 3H). [M+H] calc'd for C24H29FN6O2, 453; found, 453.

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-433df8a50bbb43a88237e2633ccc2601
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Reaction notes

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