Diisopropylethylamine → 2-(7-Chloroquinazolin-4-ylamino)-1-[3-(4-phenylpiperidin-1-yl)pyrrolidin-1-yl]ethanone

HRID 406477Notes

Reaction equation

HRID 406477 reaction equation
[NH2:1][CH2:2][C:3]([N:5]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)[CH2:6]1)=[O:4].Cl[C:23]1[C:32]2[C:27](=[CH:28][C:29]([Cl:33])=[CH:30][CH:31]=2)[N:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>C(O)CCC>[Cl:33][C:29]1[CH:28]=[C:27]2[C:32]([C:23]([NH:1][CH2:2][C:3]([N:5]3[CH2:9][CH2:8][CH:7]([N:10]4[CH2:11][CH2:12][CH:13]([C:16]5[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=5)[CH2:14][CH2:15]4)[CH2:6]3)=[O:4])=[N:24][CH:25]=[N:26]2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2418814,7-DichloroquinazolineHCID 597646952-Amino-1-[3-(4-phenylpiperidin-1-yl)pyrrolidin-1-yl]ethanone

Product 1

HCID 597648722-(7-Chloroquinazolin-4-ylamino)-1-[3-(4-phenylpiperidin-1-yl)pyrrolidin-1-yl]ethanoneYield 58.9%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2-amino-1-[3-(4-phenylpiperidin-1-yl)pyrrolidin-1-yl]ethanone (preparation #9) (0.108 g, 0.377 mmol), 4,7-dichloroquinazoline (0.075 g, 0.377 mmol) and DIEA (0.1 mL, 0.565 mmol) in n-butanol was heated in a microwave (CEM Explorer, maximum power 300 W) at about 120° C. for about 20 min. The solvent was removed in vacuo and the residue was purified by preparative RP-HPLC (20% to 50% acetonitrile/0.05M aqueous ammonium acetate, buffered to pH 4.5, over 30 min at 81 mL/min; λ=254 nm; Microsorb C18, 100 Å, 5 μm, 250×46 mm column) to yield 2-(7-chloroquinazolin-4-ylamino)-1-[3-(4-phenylpiperidin-1-yl)pyrrolidin-1-yl]ethanone (0.100 g, 0.222 mmol) as a yellow solid. RP-HPLC (Table 1, Method a) Rt 1.77 min; m/z: (M+H)+ 450.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by preparative RP-HPLC (20% to 50% acetonitrile/0.05M aqueous ammonium acetate, buffered to pH 4.5, over 30 min at 81 mL/min; λ=254 nm; Microsorb C18, 100 Å, 5 μm, 250×46 mm column)

Sources & evidence

ORD record
ord-7545b19221ed4840be23e9bd27faa9de
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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