Morpholine → HCID 57635415, compound

HRID 1971101Notes

Reaction equation

HRID 1971101 reaction equation
BrC1N2CCN(C)CC2=[C:4]([C:12]([NH:14][C@@H:15](C(C)(C)C)[C:16](NC)=[O:17])=O)N=1.[CH3:24][C:25]([CH3:53])([CH3:52])[C@H:26]([NH:31][C:32]([C:34]1[N:35]=[C:36]([C:44]#[C:45][C:46]2C=CC=CC=2)[N:37]2[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][C:38]=12)=[O:33])[C:27]([NH:29][CH3:30])=[O:28].ClC/C=C/B(O)O.C([O-])([O-])=O.[K+].[K+].N1CCOCC1>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:24][C:25]([CH3:53])([CH3:52])[C@H:26]([NH:31][C:32]([C:34]1[N:35]=[C:36](/[CH:44]=[CH:45]/[CH2:46][N:14]2[CH2:12][CH2:4][O:17][CH2:16][CH2:15]2)[N:37]2[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][C:38]=12)=[O:33])[C:27]([NH:29][CH3:30])=[O:28]

Participants

10

Reactant 5

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 6080110B-[(1E)-3-Chloro-1-propen-1-yl]boronic acidHCID 57635127HCID 57635127, compoundHCID 57635398HCID 57635398, compound

Product 1

HCID 57635415HCID 57635415, compoundYield 34%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(S)-3-bromo-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-7-methyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide (Compound 203; 0.12 g, 0.31 mmol) was dissolved in dioxane (4 mL) and (E)-3-chloroprop-1-enylboronic acid (0.037 g, 0.31 mmol) was added, followed by K2CO3 (0.11 g, 0.82 mmol), morpholine (0.054 g, 0.66 mmol) and water (0.80 mL). The resulting mixture was degassed with nitrogen and Pd(PPh3)4 (0.019 g, 0.017 mmol) was added. The mixture was subjected to microwave irradiation at 160° C. for 20 min. The mixture was diluted with EtOAc, and filtered through celite. The organic layer was concentrated, washed with water, dried over anhydrous Na2SO4, filtered and concentrated again. The residue was purified by prep LC/MS using 5-95% gradient acetonitrile/water with 0.1% formic acid to provide Compound 286 (0.035 g, 34%) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 1.07 (s, 9H), 2.52 (s, 3H), 2.81 (d, 3H), 2.89 (t, 2H), 2.97 (m, 3H), 3.28 (s, 1H), 3.58 (d, 1H), 3.99 (m, 8H), 4.35 (d, 1H), 6.11 (m, 1H), 6.68 (m, 2H), 7.71 (m, 1H); LCMS (+ESI) m/z 433.3 [M+H]+.

Workup

  1. additionwas added
  2. customirradiation at 160° C. for 20 min
  3. filtrationfiltered through celite
  4. concentrationThe organic layer was concentrated
  5. washwashed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated again
  9. customThe residue was purified by prep LC/MS

Sources & evidence

ORD record
ord-b7796c6f95f24b018e7c91ab276c954a
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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