(R)-1-(1-phenylethyl)urea → HCID 178462162, compound

HRID 588195Notes

Reaction equation

HRID 588195 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[N:9][NH:10][C:4]=2[CH:3]=1.[C:15]1([C@H:21]([NH:23][C:24]([NH2:26])=[O:25])[CH3:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CC(C)([O-])C.[K+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1COCC1>[CH3:14][S:11]([C:8]1[C:5]2[CH:6]=[N:7][C:2]([NH:26][C:24]([NH:23][C@@H:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH3:22])=[O:25])=[CH:3][C:4]=2[NH:10][N:9]=1)(=[O:13])=[O:12]

Participants

6

Reactant 3

HCID 13013340(R)-1-(1-phenylethyl)ureaHCID 23665647Potassium tert-butoxideHCID 178504857HCID 178504857, compound

Product 1

HCID 178462162HCID 178462162, compound

Reagents, catalysts & solvents 2

HCID 25112535BrettphosCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

6-Chloro-3-(methylsulfonyl)-1H-pyrazolo[4,3-c]pyridine (45 mg, 0.194 mmol), (R)-1-(1-phenylethyl)urea (38.3 mg, 0.233 mmol), and BrettPhos pre-catalyst (21.72 mg, 0.027 mmol) were taken up in THF (650 μL) in a 1.5 mL microwave vial. Potassium t-butoxide (1 M in THF, 583 μL, 0.583 mmol) was added and the vial was evacuated and back-filled with N2 (×3). The reaction mixture was stirred at 60° C. for 18 h. The crude reaction mixture was filtered through a Si-Thiol cartridge (6 mL, 500 mg) to remove excess Pd. The filtrate was concentrated in vacuo, dissolved in DMSO/MeOH (with a few drops of TFA), and purified by mass triggered, reverse phase prep-HPLC. The fractions containing pure product were concentrated in vacuo to afford (R)-1-(3-(methylsulfonyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. For C16H17N5O3S [M+1]+ 360. found 360. 1H NMR (500 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.92 (s, 1H), 7.87 (s, 1H), 7.50 (br s, 5H), 4.92-4.80 (m, 1H), 3.38 (s, 3H) 1.40 (d, J=7.0 Hz, 3H).

Workup

  1. customthe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customThe crude reaction mixture
  4. filtrationwas filtered through a Si-Thiol cartridge (6 mL, 500 mg)
  5. customto remove excess Pd
  6. concentrationThe filtrate was concentrated in vacuo
  7. dissolutiondissolved in DMSO/MeOH (with a few drops of TFA)
  8. custompurified by mass
  9. additionThe fractions containing pure product
  10. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-201089247f574af9a77d858277ab7c9c
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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