(R)-1-Boc-3-methylpiperazine → HCID 67468650, compound

HRID 1476965Notes

Reaction equation

HRID 1476965 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:21]([NH:23][CH2:24][C:25]3[C:26](=[O:33])[NH:27][C:28]([CH3:32])=[CH:29][C:30]=3[CH3:31])=[O:22])[C:11]3[C:12]([CH3:20])=[CH:13][N:14]([CH:17]([CH3:19])[CH3:18])[C:15]=3[CH:16]=2)=[CH:4][CH:3]=1.[CH3:34][C@H:35]1[NH:40][CH2:39][CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36]1.CC(C)([O-])C.[Na+]>[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O1CCOCC1>[CH3:31][C:30]1[CH:29]=[C:28]([CH3:32])[NH:27][C:26](=[O:33])[C:25]=1[CH2:24][NH:23][C:21]([C:10]1[C:11]2[C:12]([CH3:20])=[CH:13][N:14]([CH:17]([CH3:19])[CH3:18])[C:15]=2[CH:16]=[C:8]([C:5]2[CH:6]=[N:7][C:2]([N:40]3[CH2:39][CH2:38][NH:37][CH2:36][C@H:35]3[CH3:34])=[CH:3][CH:4]=2)[CH:9]=1)=[O:22]

Participants

6

Reactant 3

HCID 2756811(R)-1-Boc-3-methylpiperazineHCID 23676156Sodium t-butoxideHCID 866773496-(6-chloropyridin-3-yl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

Product 1

HCID 67468650HCID 67468650, compoundYield 18.8%

Reagents, catalysts & solvents 2

HCID 86677350Pd XPhosCatalystHCID 312751,4-DioxaneSolvent

Procedure

Added 6-(6-chloropyridin-3-yl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (131 mg, 0.283 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (70.8 mg, 0.354 mmol), sodium tert-butoxide (59.8 mg, 0.623 mmol) and 1,4-Dioxane (2 mL) to a microwave vial and degassed for 10 minutes. Added Pd XPhos (10.45 mg, 0.014 mmol) and heated to 100° C. for 16 hours. Concentrated, added DCM and water. Filtered, separated phases. Extracted aqueous phase twice more with DCM. Combined DCM extracts and washed with water, brine, dried (MgSO4), filtered and rotovapped off DCM. The residue was purified via Biotage (0% to 5% MeOH:DCM; 10 g-HP-silica gel column) Obtained 28 mg of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.16 (d, J=6.32 Hz, 3H), 1.44-1.57 (m, 15H), 2.06 (s, 3H), 2.28 (s, 3H), 2.39 (s, 3H), 2.87-3.36 (m, 3H), 3.57 (s, 1H), 3.86-4.30 (m, 3H), 4.50 (d, J=9.35 Hz, 1H), 4.58-4.79 (m, 3H), 5.87 (s, 1H), 6.64 (d, J=8.59 Hz, 1H), 7.01 (s, 1H), 7.45 (s, 1H), 7.76 (d, J=8.08 Hz, 1H), 8.46 (d, J=2.27 Hz, 1H), 12.42 (br. s., 1H). LCMS: [M+H]+ 627.5.

Workup

  1. customdegassed for 10 minutes
  2. concentrationConcentrated
  3. additionadded DCM and water
  4. filtrationFiltered
  5. customseparated phases
  6. washCombined DCM extracts and washed with water, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customThe residue was purified via Biotage (0% to 5% MeOH:DCM; 10 g-HP-silica gel column)

Sources & evidence

ORD record
ord-a5e8a7731ddf4bf5888ac9df2dfff240
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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