p-Anisoyl chloride → Tert-butyl 3-[5-ethyl-6-[4-(5,6,7,8-tetrahydro-(1,8)naphthyridin-2-yl)-piperidin-1-yl]-pyrimidin-4-ylamino]-2-(4-methoxy benzoyl)-propionate

HRID 1615967Notes

Reaction equation

HRID 1615967 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.N[CH:13]([CH2:21][NH:22][C:23]1[C:28]([CH2:29][CH3:30])=[C:27]([N:31]2[CH2:36][CH2:35][CH:34]([C:37]3[CH:46]=[CH:45][C:44]4[CH2:43][CH2:42][CH2:41][NH:40][C:39]=4[N:38]=3)[CH2:33][CH2:32]2)[N:26]=[CH:25][N:24]=1)[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]>ClCCl.N1C=CC=CC=1>[CH2:29]([C:28]1[C:23]([NH:22][CH2:21][CH:13]([C:7](=[O:8])[C:6]2[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])=[N:24][CH:25]=[N:26][C:27]=1[N:31]1[CH2:36][CH2:35][CH:34]([C:37]2[CH:46]=[CH:45][C:44]3[CH2:43][CH2:42][CH2:41][NH:40][C:39]=3[N:38]=2)[CH2:33][CH2:32]1)[CH3:30]

Participants

5

Reactant 2

HCID 7477p-Anisoyl chlorideHCID 66641143Tert-butyl 2-amino-3-{5-ethyl-6-[4-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-piperidin-1-yl]-pyrimidin-4-ylamino}-propionate

Product 1

HCID 66641286Tert-butyl 3-[5-ethyl-6-[4-(5,6,7,8-tetrahydro-(1,8)naphthyridin-2-yl)-piperidin-1-yl]-pyrimidin-4-ylamino]-2-(4-methoxy benzoyl)-propionateYield 70%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

40 mg (0.233 mmoles) of 4-methoxy-benzoyl chloride in solution in 3 ml of dichloromethane is added to a mixture of 112.5 mg (0.233 mmoles) of tert-butyl 2-amino-3-{5-ethyl-6-[4-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-piperidin-1-yl]-pyrimidin-4-ylamino}-propionate in solution in 6 ml of dichloromethane and 650 μl of pyridine. The reaction mixture is stirred at ambient temperature for 1 hour. Then, the solvent is evaporated off under reduced pressure (2 kPa) and the residue is chromatographed on silica gel with the following eluent: ethyl acetate-dichloromethane (50-50), ethyl acetate-dichloromethane/methanol (95/5) 50-50 then finishing with ethyl acetate-dichloromethane/methanol (9/1) 50-50. 98 mg of expected product is obtained.

Workup

  1. customThen, the solvent is evaporated off under reduced pressure (2 kPa)
  2. customthe residue is chromatographed on silica gel with the following eluent

Sources & evidence

ORD record
ord-569f6e44f0df4afc9a09c4c916bb94ff
Source dataset
uspto-grants-2014_07
Patent number
US08765766B2

Reaction notes

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