2,6-Dimethylmorpholine, cis- → (2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-[(2R,6S)-2,6-dimethylmorpholin-4-yl]propan-2-ol

HRID 339776Notes

Reaction equation

HRID 339776 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[N:11]=[C:10]([NH2:13])[N:9]3[CH2:14][CH2:15][N:16]=[C:8]3[C:7]=2[CH:6]=[CH:5][C:4]=1[O:17][CH2:18][C@H:19]1[CH2:21][O:20]1.[CH3:22][C@H:23]1[O:28][C@@H:27]([CH3:29])[CH2:26][NH:25][CH2:24]1>CN(C=O)C>[CH3:29][C@H:27]1[O:28][C@@H:23]([CH3:22])[CH2:24][N:25]([CH2:21][C@@H:19]([OH:20])[CH2:18][O:17][C:4]2[CH:5]=[CH:6][C:7]3[C:8]4[N:9]([CH2:14][CH2:15][N:16]=4)[C:10]([NH2:13])=[N:11][C:12]=3[C:3]=2[O:2][CH3:1])[CH2:26]1

Participants

4

Reactant 2

HCID 6415002,6-Dimethylmorpholine, cis-HCID 178493879HCID 178493879, compound2×

Product 1

HCID 178493887(2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-[(2R,6S)-2,6-dimethylmorpholin-4-yl]propan-2-olYield 96.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 7-Methoxy-8-[(2R)-oxiran-2-ylmethoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (Intermediate F, 1.50 g, 5.20 mmol) and cis-2,6-dimethylmorpholine (6.4 mL, 52.0 mmol, 10 equiv.) in DMF (36 mL) was heated in two portions in a microwave reactor for 45 min. at 140° C. The resulting combined mixtures were concentrated under reduced pressure and purified using MPLC to give N-[8-({(2R)-3-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2-hydroxypropyl}oxy)-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]amine (2.02 g, 96%): Preparative HPLC ret. time 4.29 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 1.10 (d, J=7.3 Hz, 3H), 1.14 (d, J=7.3 Hz, 3H), 2.69 (t, J=11.6 Hz, 1H), 2.76 (t, J=11.6 Hz, 1H), 3.23-3.32 (m, 2H), 3.43-3.54 (m, 2H), 3.80 (s, 3H), 3.81-3.87 (m, 1H), 3.88-3.97 (m, 1H), 4.31 (app dd, J=8.6, 12.1 Hz, 2H), 4.35-4.43 (m, 1H), 7.22 (J=9.4 Hz, 1H), 7.81 (d, J=9.1 Hz, 1H); mass spectrum m/z 404 ((M+1)+, 100%).

Workup

  1. concentrationwere concentrated under reduced pressure
  2. custompurified

Sources & evidence

ORD record
ord-ef7b305f71d64d448c002f6261faffcc
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

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