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

HRID 339782노트

반응식

HRID 339782 반응식
FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.NC1[N:25]2[CH2:26][CH2:27]N=[C:24]2[C:23]2[CH:22]=CC(O)=C(OC)C=2N=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:38][O:39][C:40]1[C:49]2[N:48]=[C:47]([NH2:50])[N:46]3[CH2:51][CH2:52][N:53]=[C:45]3[C:44]=2[CH:43]=[CH:42][C:41]=1[O:54][CH2:55][C@H:56]1[CH2:58][O:57]1.N1CCCCC1>CN(C=O)C>[OH:57][C@H:56]([CH2:58][N:25]1[CH2:24][CH2:23][CH2:22][CH2:27][CH2:26]1)[CH2:55][O:54][C:41]1[CH:42]=[CH:43][C:44]2[C:45]3[N:46]([CH2:51][CH2:52][N:53]=3)[C:47]([NH2:50])=[N:48][C:49]=2[C:40]=1[O:39][CH3:38]

참가 물질

6

반응물 4

HCID 8082PiperidineHCID 10796Cesium carbonateHCID 178493836HCID 178493836, 화합물2회HCID 178493879HCID 178493879, 화합물2회

생성물 1

HCID 178493885(2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-piperidin-1-ylpropan-2-ol수율 79.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a slurry of 5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-ol bis(trifluoroacetate) (Intermediate E, 3.00 g, 6.52 mmol) in DMF (72 mL) was added caesium carbonate (10.62 g, 32.6 mmol, 10.0 equiv.) and the resulting slurry was stirred at room temperature for 1.5 hr, followed by the addition of (R)-glycidyl methanesulfonate (Intermediate F, Step 1, 45 mL, 0.29 M in DMF, 13.0 mmol, 2.0 equiv.). This mixture was stirred at 60° C. for 12 hr and concentrated under reduced pressure to a volume of approximately 50 mL and divided into 3 portions. Each portion was treated with 2.15 mL piperidine (6.45 mL total, 65.2 mmol, 10 equiv.) and was heated in a microwave reactor for 45 min. at 140° C. The combined resulting mixtures were concentrated under reduced pressure. The resulting solids (1.93 g) were purified by MPLC to give N-(8-{[(2R)-2-hydroxy-3-(piperidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)amine (1.93 g, 79%): 1H NMR (DMSO-d6+1 drop TFA-d) δ 1.30-1.43 (m, 1H), 1.56-1.70 (m, 2H), 1.70-1.84 (m, 2H), 2.88-3.04 (m, 2H), 3.11-3.32 (m, 2H), 3.42-3.52 (m, 2H), 3.82 (s, 3H), 4.09-4.17 (m, 4H), 4.28-4.38 (m, 3H), 7.24 (d, J=9.4 Hz, 1H), 7.83 (d, J=9.1 Hz, 1H).

후처리

  1. stirringThis mixture was stirred at 60° C. for 12 hr
  2. concentrationconcentrated under reduced pressure to a volume of approximately 50 mL
  3. temperaturewas heated in a microwave reactor for 45 min. at 140° C
  4. customThe combined resulting mixtures
  5. concentrationwere concentrated under reduced pressure
  6. customThe resulting solids (1.93 g) were purified by MPLC

출처 및 근거

ORD 기록
ord-03914478ff6e4e6e9dea74bcd6d98c1f
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895549B2

반응 노트

불러오는 중…