Triethylamine → 6-(3-Fluorophenyl)-N-(1-(5-methoxy-2-(pyridin-2-yl)pyrimidin-4-yl)piperidin-4-yl)nicotinamide

HRID 602083Notes

Reaction equation

HRID 602083 reaction equation
[F-].[Cs+].Cl[C:4]1[C:9]([O:10][CH3:11])=[CH:8][N:7]=[C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14]C=2)[N:5]=1.Cl.[F:19][C:20]1[CH:21]=[C:22]([C:26]2[CH:40]=[CH:39][C:29]([C:30]([NH:32][CH:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[O:31])=[CH:28][N:27]=2)[CH:23]=[CH:24][CH:25]=1.C([N:43](CC)CC)C>CN(C=O)C>[F:19][C:20]1[CH:21]=[C:22]([C:26]2[CH:40]=[CH:39][C:29]([C:30]([NH:32][CH:33]3[CH2:34][CH2:35][N:36]([C:4]4[C:9]([O:10][CH3:11])=[CH:8][N:7]=[C:6]([C:12]5[CH:17]=[CH:16][CH:15]=[CH:14][N:43]=5)[N:5]=4)[CH2:37][CH2:38]3)=[O:31])=[CH:28][N:27]=2)[CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 25953Cesium fluorideHCID 43260394-Chloro-5-methoxy-2-phenylpyrimidineHCID 672680466-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide hydrochloride

Product 1

HCID 597438906-(3-Fluorophenyl)-N-(1-(5-methoxy-2-(pyridin-2-yl)pyrimidin-4-yl)piperidin-4-yl)nicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
87.5 °C

Procedure

To a vial containing CsF (60-85 mgs, 5-7 eqs) was added (0.2 mL, 0.08 mmol) of a solution of 4-chloro-5-methoxy-2-phenylpyrimidine in DMF followed by addition of (0.22 mL, 0.088 mmol) of 6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide-HCl salt in DMF and triethylamine (2-3 eq). The reaction mixture was heated to 85-90° C. for 24 hrs and then allowed to cool to room temperature. The crude reaction mixture was then filtered and purified by RP-HPLC to give the desired product. 1H NMR (400 MHz, DMSO-d6) □ ppm 1.63-1.73 (m, 2H) 1.96 (d, J=10.25 Hz, 2H) 3.11-3.19 (m, 2H) 3.94 (s, 3 H) 4.18 (d, J=7.69 Hz, 1H) 4.64 (d, J=12.81 Hz, 2H) 7.31 (td, J=8.33, 2.38 Hz, 1H) 7.43 (d, J=5.12 Hz, 1 H) 7.53-7.59 (m, 1H) 7.87-7.97 (m, 2H) 8.00 (d, J=7.69 Hz, 1H) 8.12 (d, J=8.42 Hz, 1H) 8.20 (s, 1H) 8.26 (d, J=8.05 Hz, 1H) 8.29 (dd, J=8.42, 1.83 Hz, 1H) 8.50 (d, J=7.69 Hz, 1H) 8.68 (d, J=4.39 Hz, 1H) 9.08 (s, 1H); LC/MS(ES+)=485.5 observed, 485.21 expected.

Workup

  1. temperatureto cool to room temperature
  2. customThe crude reaction mixture
  3. filtrationwas then filtered
  4. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-21c590ca03bf4d55bdc212e3dc6dd332
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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