Triethylamine → 4-(8-(benzo[d][1,3]dioxol-5-ylmethyl)-8-aza-bicyclo[3.2.1]octan-3-ylamino)-6-chloro-1-(2,2,2-trifluoroethyl)quinazolin-2(1H)-one

HRID 897263Notes

Reaction equation

HRID 897263 reaction equation
[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]([NH:9][C:10]1[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=3)[N:13]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:12](=[O:26])[N:11]=1)[CH2:2]2.C(N(CC)CC)C.Cl[CH2:35][C:36]1[CH:44]=[CH:43][C:39]2[O:40][CH2:41][O:42][C:38]=2[CH:37]=1>CN(C=O)C>[O:40]1[C:39]2[CH:43]=[CH:44][C:36]([CH2:35][N:8]3[CH:5]4[CH2:6][CH2:7][CH:1]3[CH2:2][CH:3]([NH:9][C:10]3[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=5)[N:13]([CH2:21][C:22]([F:24])([F:25])[F:23])[C:12](=[O:26])[N:11]=3)[CH2:4]4)=[CH:37][C:38]=2[O:42][CH2:41]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 887131,3-Benzodioxole, 5-(chloromethyl)-HCID 223480694-(8-Aza-bicyclo[3.2.1]oct-3-ylamino)-6-chloro-1-(2,2,2-trifluoro-ethyl)-1H-quinazolin-2-One

Product 1

HCID 100753754-(8-(benzo[d][1,3]dioxol-5-ylmethyl)-8-aza-bicyclo[3.2.1]octan-3-ylamino)-6-chloro-1-(2,2,2-trifluoroethyl)quinazolin-2(1H)-oneYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(8-aza-bicyclo[3.2.1]oct-3-ylamino)-6-chloro-1-(2,2,2-trifluoro-ethyl)-1H-quinazolin-2-one (149 mg, 0.320 mmol) in DMF (10 mL) was added triethylamine (0.3 mL) and 5-Chloromethyl-benzo[1,3]dioxole (0.061 mL, 0.480 mmol). The solution was heated to 50° C. and stirred for 6 hrs. The reaction was partitioned between ethyl acetate and water and the organic phase was washed an additional 2× with water and brine, dried over Na2SO4, filtered, and concentrated. The crude residue was purified by flash chromatography (gradient elution: 0→20% MeOH/dichloromethane) to provide 99 mg white solid (60%). 1H NMR (300 MHz, CDCl3) δ ppm 2.10 (m, 4H), 2.32 (m, 2H), 3.56 (m, 3H), 3.77 (s, 2H), 4.87 (m, 2H), 5.96 (s, 2H), 6.77 (d, J=8.0 Hz, 1H), 6.83 (m, 1H), 6.95 (d, J=8.1 Hz, 1H), 7.17 (m, 2H), 7.56 (dd, J=2.3, 8.9 Hz, 1H), 7.91 (s, 1H); MS (ESI+Q1MS) m/z 522 [M+2H]+

Workup

  1. customThe reaction was partitioned between ethyl acetate and water
  2. washthe organic phase was washed an additional 2× with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography (gradient elution: 0→20% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-df8d3eee51504ec4a1407a88f4f02f9c
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

Loading…