Diisopropylethylamine → (S)-4-(5-chloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-methylmorpholine

HRID 72181

반응식

HRID 72181 반응식
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[N:10]([CH3:11])[N:9]=[CH:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.[CH3:22][C@H:23]1[CH2:28][O:27][CH2:26][CH2:25][NH:24]1>CN(C=O)C.CCOCC>[Cl:1][C:2]1[N:3]=[C:4]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][C@@H:23]2[CH3:22])[C:5]2[N:10]([CH3:11])[N:9]=[CH:8][C:6]=2[N:7]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 12012220(3S)-3-methylmorpholineHCID 574158625,7-dichloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidine

생성물 1

HCID 58222518(S)-4-(5-chloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-methylmorpholine수율 93.5%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of 5,7-dichloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidine (200.0 mg, 0.98 mmol) in anhydrous DMF (2 mL) was added N,N-diisopropylethylamine (0.21 mL, 1.18 mmol, 1.2 eq.) followed by (S)-3-methylmorpholine (199.3 mg, 1.9 mmol, 2.0 eq.). The reaction mixture was stirred at RT under N2 for 4 h and diluted with ether (50 mL). The organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane) to afford the desired product (k-1) as a foam (245.4 mg, 93.0%). 1H NMR (CDCl3, 500 MHz) δ ppm 8.03 (s, 1H), 4.21 (broad d, J=6.2 Hz, 1H), 4.15 (s, 3H), 3.97 (d, J=10.7 Hz, 1H), 3.90 (d, J=9.8 Hz, 1H), 3.81 to 3.65 (m, 3H), 3.56 (d, J=12.4 Hz, 1H), 1.38 (d, J=6.6 Hz, 3H); LC-MS m/z (method A)=268 [M+H]+, RT=1.71 min.

후처리

  1. washThe organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-6509c6b03059425bb28feba1c042a567
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828990B2

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