4-Aminotetrahydropyran → HCID 76901356, compound

HRID 880320Notes

Reaction equation

HRID 880320 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:24]=1)[C:7]([NH:9][CH2:10][CH:11]([OH:23])[CH2:12][N:13]1[CH2:22][CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14]1)=[O:8].[O:25]1[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27][CH2:26]1.CC([O-])(C)C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:21][CH2:22][N:13]1[CH2:12][CH:11]([OH:23])[CH2:10][NH:9][C:7](=[O:8])[C:6]1[CH:24]=[C:2]([NH:31][CH:28]2[CH2:29][CH2:30][O:25][CH2:26][CH2:27]2)[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 4192234-AminotetrahydropyranHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 90241532HCID 90241532, compound

Product 1

HCID 76901356HCID 76901356, compoundYield 24.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-bromo-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)nicotinamide (100 mg, 0.26 mmol) in dioxane (10 mL) were added tetrahydro-2H-pyran-4-amine (39.4 mg, 0.29 mmol), Pd2(dba)3 (20 mg, 0.02 mmol), NaOtBu (24 mg, 0.52 mmol) and BINAP (26 mg, 0.04 mmol). The reaction mixture was heated at 110° C. for 6 h under N2. The mixture was concentrated and the residue was dissolved in EA, washed with water, the organic layer was collected, dried, and the residue purified by prep-HPLC to give the title compound (25.9 mg, Yield 24%). 1H NMR (CD3OD, 400 MHz): δ 8.17 (d, J=1.5 Hz, 1H), 8.05 (d, J=2.5 Hz, 1H), 7.43-7.35 (m, 1H), 7.13-7.06 (m, 3H), 7.04-6.99 (m, 1H), 4.17-4.07 (m, 1H), 4.02-3.93 (m, 2H), 3.73 (s, 2H), 3.63-3.50 (m, 4H), 3.41 (dd, J=6.8, 13.6 Hz, 1H), 2.94-2.82 (m, 4H), 2.70-2.57 (m, 2H), 2.03-1.93 (m, 2H), 1.57-1.45 (m, 2H). LCMS (m/z): 411.1 (M+1).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in EA
  3. washwashed with water
  4. customthe organic layer was collected
  5. customdried
  6. customthe residue purified by prep-HPLC

Sources & evidence

ORD record
ord-e3950b01d3ad49e3a039c16486e0eb29
Source dataset
uspto-grants-2015_03
Patent number
US08993555B2

Reaction notes

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