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

HRID 590797Notes

Reaction equation

HRID 590797 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([NH:30][CH2:31][CH3:32])=[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:33]1([C@H:39]([NH:41][C:42]([NH2:44])=[O:43])[CH3:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1COCC1>[CH2:31]([NH:30][C:8]1[C:5]2[CH:6]=[N:7][C:2]([NH:44][C:42]([NH:41][C@@H:39]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH3:40])=[O:43])=[CH:3][C:4]=2[N:10]([C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]=1)[CH3:32]

Participants

6

Reactant 3

HCID 13013340(R)-1-(1-phenylethyl)ureaHCID 23676156Sodium t-butoxideHCID 1182720066-chloro-N-ethyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine

Product 1

HCID 118272409(R)-1-(3-(ethylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 2

HCID 25112535BrettphosCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

6-Chloro-N-ethyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine (3 g, 6.83 mmol), (R)-1-(1-phenylethyl)urea (1.68 g, 10.25 mmol), and BrettPhos pre-catalyst (546 mg, 0.68 mmol) were taken up in THF (13 mL). The resulting mixture was degassed for 5 min followed by addition of sodium tert-butoxide (6834 μL, 13.67 mmol) at room temperature. After the mixture was degassed again for 5 min, the reaction was heated to 50° C. under N2 for 6 h, Room temperature was attained, sat NH4Cl was added, and the mixture was extracted with EtOAc. The organic layer was washed with water, dried, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (0-100% EtOAc/Hexanes) gave (R)-1-(3-(ethylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. For C36H34N6O [M+1]+ 567. found 567.

Workup

  1. customThe resulting mixture was degassed for 5 min
  2. customAfter the mixture was degassed again for 5 min
  3. additionwas added
  4. extractionthe mixture was extracted with EtOAc
  5. washThe organic layer was washed with water
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by flash chromatography (0-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-b4d0435d1a5b449fbef3d50139655292
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

Loading…