Cesium carbonate → (R)-methyl (6-(3-(1-(4-fluorophenyl)ethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)carbamate

HRID 590871ノート

反応式

HRID 590871 の反応式
[C:1](=O)([O-])[O-].[Cs+].[Cs+].Cl[C:8]1[N:13]=[CH:12][C:11]2[C:14]([NH:36][C:37](=[O:39])[O-:38])=[N:15][N:16](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:10]=2[CH:9]=1.[F:40][C:41]1[CH:46]=[CH:45][C:44]([C@H:47]([NH:49][C:50]([NH2:52])=[O:51])[CH3:48])=[CH:43][CH:42]=1.C1(P(C2CCCCC2)C2C(OC)=CC=C(OC)C=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([SiH](CC)CC)C>O1CCOCC1>[F:40][C:41]1[CH:42]=[CH:43][C:44]([C@H:47]([NH:49][C:50](=[O:51])[NH:52][C:8]2[N:13]=[CH:12][C:11]3[C:14]([NH:36][C:37](=[O:39])[O:38][CH3:1])=[N:15][NH:16][C:10]=3[CH:9]=2)[CH3:48])=[CH:45][CH:46]=1

参加物

7

反応物 5

HCID 10796Cesium carbonateHCID 12052TriethylsilaneHCID 25112535BrettphosHCID 117601722(R)-1-(1-(4-fluorophenyl)ethyl)ureaHCID 131734498(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)carbamate

生成物 1

HCID 73505652(R)-methyl (6-(3-(1-(4-fluorophenyl)ethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)carbamate

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A 5 mL microwave vial was charged with cesium carbonate (71.7 mg, 0.220 mmol), (6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)carbamate (40 mg, 0.085 mmol), (R)-1-(1-(4-fluorophenyl)ethyl)urea (23.3 mg, 0.128 mmol), 2-(dicyclohexylphosphino)3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl (3.21 mg, 5.97 μmol) and BrettPhos-G3-Pd (5.41 mg, 5.97 μmol). Dioxane (1 ml) was added, the vial was flushed with argon, capped and the contents heated to 100° C. with stirring for 16 h. The reaction mixture was diluted with DCM (2 ml), MP-TMT (119 mg, 0.119 mmol) added and the contents heated to 65° C. for 4 h with shaking. The reaction mixture was filtered, washing through with DCM (2 mL) and concentrated. The resulting residue was re-dissolved in TFA (1 mL) and stirred at room temperature for 30 minutes. Triethylsilane (0.014 ml, 0.085 mmol) was added drop wise and the reaction mixture was stirred for an additional 5 minutes. The volatiles were removed in vacuo, the resulting residue was re-dissolved in DMSO (1.5 mL) and submitted for purification by mass-triggered HPLC to afford (R)-methyl (6-(3-(1-(4-fluorophenyl)ethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)carbamate. TFA (5.4 mg, 0.011 mmol, 13.1% yield) as a white solid. MS ESI calc'd. For C17H18FN6O3 [M+H]+ 373. found 373. 1H NMR (ppm, 600 MHz, DMSO-d6): δ 10.39 (s, 1H); 9.26 (s, 1H); 8.94 (s, 1H); 7.76 (s, 1H); 7.43 (s, 1H); 7.35 (dd, J=8.4, 5.5 Hz, 2H); 7.13 (t, J=8.8 Hz, 2H); 4.84 (t, J=7.2 Hz, 1H); 3.68 (s, 3H); 1.37 (d, J=7.0 Hz, 3H).

後処理

  1. customthe vial was flushed with argon
  2. customcapped
  3. additionThe reaction mixture was diluted with DCM (2 ml), MP-TMT (119 mg, 0.119 mmol)
  4. additionadded
  5. temperaturethe contents heated to 65° C. for 4 h
  6. stirringwith shaking
  7. filtrationThe reaction mixture was filtered
  8. washwashing through with DCM (2 mL)
  9. concentrationconcentrated
  10. dissolutionThe resulting residue was re-dissolved in TFA (1 mL)
  11. stirringstirred at room temperature for 30 minutes
  12. stirringthe reaction mixture was stirred for an additional 5 minutes
  13. customThe volatiles were removed in vacuo
  14. dissolutionthe resulting residue was re-dissolved in DMSO (1.5 mL)
  15. customsubmitted for purification by mass-triggered HPLC

出典と根拠

ORDレコード
ord-b11a8df8269845c2b9817a4a7567e680
出典データセット
uspto-grants-2016_01
特許番号
US09233979B2

反応ノート

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