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

HRID 571395Notes

Reaction equation

HRID 571395 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)=[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.[C:37]1([C@H:43]([NH:45][C:46]([NH2:48])=[O:47])[CH3:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=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.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].CC(N(C)C)=O>[F:36][C:33]1[CH:32]=[CH:31][C:30]([C:8]2[C:5]3[CH:6]=[N:7][C:2]([NH:48][C:46]([NH:45][C@@H:43]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[CH3:44])=[O:47])=[CH:3][C:4]=3[N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:9]=2)=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 13013340(R)-1-(1-phenylethyl)ureaHCID 895258266-chloro-3-(4-fluorophenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine2×

Product 1

HCID 89525854(R)-1-(3-(4-fluorophenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)ureaYield 92.5%

Reagents, catalysts & solvents 2

HCID 25112666BrettPhos PalladacycleCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

6-chloro-3-(4-fluorophenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (Intermediate 4a, 73 mg, 0.147 mmol), (R)-1-(1-phenylethyl)urea (37 mg, 0.225 mmol), Cs2CO3 (120 mg, 0.367 mmol), BrettPhos precatalyst (11.7 mg, 0.015 mmol) and DMA (1.1 mL) were charged in a vial. The mixture was evacuated and purged with nitrogen six times and heated at 100° C. for 55 min. The mixture was diluted with EtOAc and washed with water, brine, dried (Na2SO4) and concentrated to afford a residue, which was purified by chromatography on silica gel (0-100% ethyl acetate in hexane, 20 CV) to afford (R)-1-(3-(4-fluorophenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (85 mg, 0.136 mmol, 92%) as a yellow solid. MS ESI calcd. For C40H32FN5O [M+H]+ 618, found 618.

Workup

  1. customThe mixture was evacuated
  2. custompurged with nitrogen six times
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with water, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto afford a residue, which
  8. customwas purified by chromatography on silica gel (0-100% ethyl acetate in hexane, 20 CV)

Sources & evidence

ORD record
ord-a92a47b0f18344d082f229cfb3a301a0
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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