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

HRID 588209Notes

Reaction equation

HRID 588209 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][OH:9])[C:5]2[C:10]([O:32][CH3:33])=[N:11][N:12]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:40]1([C@H:46]([NH:48][C:49]([NH2:51])=[O:50])[CH3:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>O1CCOCC1.C(Cl)Cl.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+]>[OH:9][CH2:8][C:6]1[C:5]2[C:10]([O:32][CH3:33])=[N:11][N:12]([C:13]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:4]=2[CH:3]=[C:2]([NH:51][C:49]([NH:48][C@@H:46]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH3:47])=[O:50])[N:7]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 13013340(R)-1-(1-phenylethyl)ureaHCID 118271763(6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanol

Product 1

HCID 118271829(R)-1-(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 3

HCID 25112666BrettPhos PalladacycleCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-i-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(ii) (67.5 mg, 0.084 mmol), (6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanol (35B, 385 mg, 0.844 mmol), cesium carbonate (825 mg, 2.53 mmol) and (R)-1-(1-phenylethyl)urea (277 mg, 1.689 mmol) were taken up in dioxane (5 ml) in a 1.5 mL microwave vial and the vial was evacuated and back-filled with N2 (×3). The reaction mixture was stirred at 90° C. for 2 hours. The crude reaction mixture was diluted with DCM and filtered through syringe filter. The filtrate was concentrated, and purified on 80 g Redsep gold silica gel 5-25% DCM/EtOAc to provide (R)-1-(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS: [M+H]+ m/z 584.

Workup

  1. customthe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customThe crude reaction mixture
  4. filtrationfiltered through syringe
  5. filtrationfilter
  6. concentrationThe filtrate was concentrated
  7. custompurified on 80 g Redsep gold silica gel 5-25% DCM/EtOAc

Sources & evidence

ORD record
ord-03401f0d67a1488db0b8b845dcb45885
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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