Diisopropylethylamine → 5-chloro-N-[2-methoxy-4-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842709

반응식

HRID 1842709 반응식
Cl.Cl.[CH3:3][N:4]1[CH2:11][CH2:10][CH2:9][C:5]21[CH2:8][NH:7][CH2:6]2.[Cl:12][C:13]1[C:14]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:15][C:16]([NH:19][C:20]2[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[C:23](F)=[CH:22][C:21]=2[O:30][CH3:31])=[N:17][CH:18]=1.CN1CCCC21CNC2.CCN(C(C)C)C(C)C>CO.O.CC(N(C)C)=O.CO>[Cl:12][C:13]1[C:14]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:15][C:16]([NH:19][C:20]2[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[C:23]([N:7]3[CH2:8][C:5]4([CH2:9][CH2:10][CH2:11][N:4]4[CH3:3])[CH2:6]3)=[CH:22][C:21]=2[O:30][CH3:31])=[N:17][CH:18]=1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 712393485-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2회HCID 717431205-Methyl-2,5-diazaspiro[3.4]octane dihydrochloride2회HCID 717431215-Methyl-2,5-diazaspiro[3.4]octane

생성물 1

HCID 712407855-chloro-N-[2-methoxy-4-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine수율 85.4%

시약·촉매·용매 3

HCID 887Methanol용매2회HCID 31374Dimethylacetamide용매HCID 22242641Methanol--water (1/1)용매

반응 조건

온도
140 °C

실험 절차

A mixture of 5-methyl-2,5-diazaspiro[3.4]octane dihydrochloride salt (Intermediate 47, 400 mg) in CH3OH/water was absorbed onto an SCX column. The column was washed with CH3OH and eluted with methanolic ammonia. The fractions containing product were combined and concentrated (caution: product is volatile). A mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 250 mg, 0.60 mmol), 5-methyl-2,5-diazaspiro[3.4]octane (91 mg, 0.72 mmol) and DIPEA (0.365 mL, 2.11 mmol) in DMA (3 mL) was heated at 140° C. for 0.5 h in a microwave. The mixture was then diluted with CH3OH and absorbed onto an SCX column. The column was washed with CH3OH and eluted with 1:1 methanolic ammonia in CH2Cl2. Fractions containing the product were combined and concentrated to provide a solid. This solid was suspended in CH3OH, filtered, washed with diethyl ether and dried to give the title compound (267 mg, 85%) as a red solid; 1H NMR: 1.63-1.78 (2H, m), 2-2.12 (2H, m), 2.41 (3H, s), 2.69 (2H, t), 3.77 (2H, d), 3.90 (3H, s), 4.13 (2H, d), 6.30 (1H, s), 7.14 (1H, td), 7.34 (1H, t), 8.12 (1H, s), 8.41-8.46 (2H, m), 8.74 (1H, s), 8.86 (1H, d), 8.96 (1H, s); m/z: ES+ MH+ 521.46.

후처리

  1. customwas absorbed onto an SCX column
  2. washThe column was washed with CH3OH
  3. washeluted with methanolic ammonia
  4. additionThe fractions containing product
  5. concentrationconcentrated (caution: product is volatile)
  6. customabsorbed onto an SCX column
  7. washThe column was washed with CH3OH
  8. washeluted with 1:1 methanolic ammonia in CH2Cl2
  9. additionFractions containing the product
  10. concentrationconcentrated
  11. customto provide a solid
  12. filtrationfiltered
  13. washwashed with diethyl ether
  14. customdried

출처 및 근거

ORD 기록
ord-283dded0f08549108c49aafc9ee7e931
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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