Cesium carbonate → (S)-1-(2-methoxy-1-phenylethyl)-3-(3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

HRID 588178Notes

Reaction equation

HRID 588178 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH3:31])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[CH3:32][O:33][CH2:34][C@@H:35]([NH:42][C:43]([NH2:45])=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.O1CCOCC1>[CH3:32][O:33][CH2:34][C@@H:35]([NH:42][C:43]([NH:45][C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH3:31])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 89524417(S)-1-(2-methoxy-1-phenylethyl)urea2×HCID 1182718976-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 118272566(S)-1-(2-methoxy-1-phenylethyl)-3-(3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

Reagents, catalysts & solvents 2

HCID 25112535BrettphosCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-Chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine (Example 40, Step 1; 151 mg, 0.355 mmol), (S)-1-(2-methoxy-1-phenylethyl)urea (Intermediate 16B; 108 mg, 0.556 mmol), BrettPhos pre-catalyst (17.6 mg, 0.022 mmol), and cesium carbonate (337 mg, 1.034 mmol) were taken up in 1,4-dioxane (3.5 mL) in a 5 mL microwave vial. The vial was evacuated and back-filled with N2 (×3) and the reaction stirred at 100° C. for 6 h. Room temperature was attained, the reaction mixture was filtered through Celite, eluting with MeOH, and the filtrate was concentrated in vacuo. Purification of the residue by flash chromatography (6-50% EtOAc-hexanes) gave (S)-1-(2-methoxy-1-phenylethyl)-3-(3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea. MS ESI calc'd. For C36H33N5O3 [M+1]+ 584. found 584.

Workup

  1. customThe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customRoom temperature
  4. filtrationthe reaction mixture was filtered through Celite
  5. washeluting with MeOH
  6. concentrationthe filtrate was concentrated in vacuo
  7. customPurification of the residue by flash chromatography (6-50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-58a08abd02334592b53edb53e9634bd7
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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