Cesium carbonate → (R)-1-(3-ethyl-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-(1-phenylethyl)urea

HRID 590848Notes

Reaction equation

HRID 590848 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[N:12]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:13]=[C:8]3[C:9]2=[C:4]([CH2:5][CH2:6][N:7]3[CH2:33][CH3:34])[N:3]=1.[C:35]1([C@H:41]([NH:43][C:44]([NH2:46])=[O:45])[CH3:42])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=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.C(Cl)Cl>[CH2:33]([N:7]1[CH2:6][CH2:5][C:4]2[N:3]=[C:2]([NH:46][C:44]([NH:43][C@@H:41]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH3:42])=[O:45])[CH:11]=[C:10]3[N:12]([C:14]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:13]=[C:8]1[C:9]=23)[CH3:34]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 13013340(R)-1-(1-phenylethyl)ureaHCID 1182718767-Chloro-3-ethyl-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine

Product 1

HCID 118272227(R)-1-(3-ethyl-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 2

HCID 25112535BrettphosCatalystHCID 6344DichloromethaneSolvent

Procedure

7-chloro-3-ethyl-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine (35 mg, 0.075 mmol), (R)-1-(1-phenylethyl)urea (18.5 mg, 0.113 mmol), cesium carbonate (73.6 mg, 0.226 mmol) and BrettPhos pre-catalyst (6.8 mg) were charged in a 1 dram vial, evacuated and backfilled with nitrogen and taken in 1,4-dioxane (0.4 mL) and heated reaction at 100° C. for 1 hour. The reaction mixture was diluted with DCM, washed with water, brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-75% EtOAc-hexanes) gave (R)-1-(3-ethyl-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. for C38H36N6O [M+H]+ 593. found 593.

Workup

  1. customevacuated
  2. temperatureheated
  3. customreaction at 100° C. for 1 hour
  4. washwashed with water, brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customPurification of the residue by flash column (0-75% EtOAc-hexanes)

Sources & evidence

ORD record
ord-98a492cfaa954decb71a78b8867f0aa3
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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