HCID 58547844, compound → HCID 58547787, compound

HRID 2207847Notes

Reaction equation

HRID 2207847 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[C:8]([O:21][CH:22]3[CH2:25][N:24]([C:26]4[CH:35]=[CH:34][C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[N:27]=4)[CH2:23]3)=[N:9][C:10]([N:13]3[CH2:18][CH2:17][CH:16]([CH2:19][OH:20])[CH2:15][CH2:14]3)=[N:11][CH:12]=2)[CH2:3][CH2:2]1>CO.[Pd]>[N:27]1[C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:34]=[CH:35][C:26]=1[N:24]1[CH2:25][CH:22]([O:21][C:8]2[C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[CH:12][N:11]=[C:10]([N:13]3[CH2:18][CH2:17][CH:16]([CH2:19][OH:20])[CH2:15][CH2:14]3)[N:9]=2)[CH2:23]1

Participants

4

Reactant 1

HCID 58547844HCID 58547844, compound

Product 1

HCID 58547787HCID 58547787, compoundYield 90.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of (1-(5-(3,6-dihydro-2H-pyran-4-yl)-4-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-2-yl)piperidin-4-yl)methanol (100 mg, 0.21 mmol) and wet Pd—C (50%, 50 mg) in MeOH (10 mL) was stirred under H2 (30 psi) at room temperature for 6 hours then the reaction mixture was filtered through CELITE® and washed with MeOH. The filtrate was concentrated in vacuo to give (1-(4-((1-(quinolin-2-yl)azetidin-3-yl)oxy)-5-(tetrahydro-2H-pyran-4-yl)pyrimidin-2-yl)piperidin-4-yl)methanol (90 mg, 0.19 mmol, yield 90%). ESI-MS (M+1): 476 calc. for C27H33N5O3 475. PDE10 IC50 (uM): 0.0029 1H NMR (CDCl3, 400 MHz) δ (ppm): 8.23 (d, J=9.2 Hz, 1H); 8.08-8.06 (m, 1H); 7.95-7.93 (m, 1H); 7.80-7.78 (m, 2H); 7.55-7.51 (m, 1H); 6.74-6.70 (m, 1H); 5.73-5.72 (m, 1H); 5.19-5.10 (m, 2H); 4.70-4.51 (m, 4H); 4.27 (d, J=6.4 Hz, 1H); 4.08-4.06 (m, 2H); 3.57-3.48 (m, 3H); 3.20-3.14 (m, 2H); 2.89-2.88 (m, 1H); 2.02-1.93 (m, 3H); 1.78-1.76 (m, 4H); 1.42-4.37 (m, 2H).

Workup

  1. filtrationthe reaction mixture was filtered through CELITE®
  2. washwashed with MeOH
  3. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-e9568d001bc74496bb5320ed64e6abf2
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

Loading…