Pyrrolidine → (2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-pyrrolidin-1-ylpropan-2-ol

HRID 339780Notes

Reaction equation

HRID 339780 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.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>CN(C=O)C>[OH:20][C@H:19]([CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:18][O:17][C:4]1[CH:5]=[CH:6][C:7]2[C:8]3[N:9]([CH2:14][CH2:15][N:16]=3)[C:10]([NH2:13])=[N:11][C:12]=2[C:3]=1[O:2][CH3:1]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 178493879HCID 178493879, compound2×

Product 1

HCID 178493883(2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-pyrrolidin-1-ylpropan-2-olYield 78%

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, 1.00 g, 3.47 mmol) and pyrrolidine (2.87 mL, 34.7 mmol, 10 equiv.) in DMF (18 mL) was in a microwave reactor for 45 min. at 140° C. The resulting mixture was concentrated under reduced pressure. The residue (2.5 g) was purified using MPLC to give N-(8-{[(2R)-2-hydroxy-3-(pyrrolidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)amine (0.97 g, 78%): HPLC ret. time 0.71 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 1.82-1.92 (m, 2H), 1.94-2.03 (m, 2H), 3.02-3.14 (m, 3H), 3.27-3.33 (m, 2H), 3.52-3.61 (m, 2H), 3.80 (s, 3H), 4.06-4.16 (m, 4H), 4.23 (br sextet, J=4.3 Hz, 1H), 4.28-4.34 (m, 2H), 7.22 (d, J=9.4 Hz, 1H), 7.81 (d, J=9.1 Hz, 1H); mass spectrum m/z 360 ((M+1)+, 100%).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. customThe residue (2.5 g) was purified

Sources & evidence

ORD record
ord-696d4347c7064394ad0bf44cd6db95bc
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

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