8-Oxa-3-aza-bicyclo(3.2.1)octane hydrochloride → (2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)propan-2-ol

HRID 339778Notes

Reaction equation

HRID 339778 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.Cl.[CH:23]12[O:30][CH:27]([CH2:28][CH2:29]1)[CH2:26][NH:25][CH2:24]2>CN(C=O)C>[OH:20][C@H:19]([CH2:21][N:25]1[CH2:24][CH:23]2[O:30][CH:27]([CH2:28][CH2:29]2)[CH2:26]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 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 178493879HCID 178493879, compound2×

Product 1

HCID 178493880(2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)propan-2-olYield 271.1%

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, 0.195 g, 0.68 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (0.506 g, 3.38 mmol, 10 equiv.) in DMF (4.5 mL) was heated in a microwave reactor for 45 min. at 140° C. The resulting mixture was concentrated under reduced pressure. The residue was treated with a 4:1 CH2Cl2/isopropanol solution (25 mL), washed with a saturated sodium bicarbonate solution (25 mL), dried (anh. sodium sulfate) and concentrated under reduced pressure. The resulting residue was purified using MPLC to give N-(8-{[(2R)-2-hydroxy-3-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-ylamine (0.74 g, 16%): HPLC ret. time 0.70 min.; mass spectrum m/z 402 ((M+1)+, 7%).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. additionThe residue was treated with a 4:1 CH2Cl2/isopropanol solution (25 mL)
  3. washwashed with a saturated sodium bicarbonate solution (25 mL)
  4. dry with materialdried (anh. sodium sulfate)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified

Sources & evidence

ORD record
ord-21e0b6d994e74645a39bccb3401d872b
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

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