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

HRID 590837Notes

Reaction equation

HRID 590837 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][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[N:3]=1.[C:42]1([C@H:48]([NH:50][C:51]([NH2:53])=[O:52])[CH3:49])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=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>[CH3:41][O:40][C:37]1[CH:36]=[CH:35][C:34]([CH2:33][N:7]2[CH2:6][CH2:5][C:4]3[N:3]=[C:2]([NH:53][C:51]([NH:50][C@@H:48]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)[CH3:49])=[O:52])[CH:11]=[C:10]4[N:12]([C:14]([C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=5)([C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=5)[C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=5)[N:13]=[C:8]2[C:9]=34)=[CH:39][CH:38]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 13013340(R)-1-(1-phenylethyl)ureaHCID 1182723927-Chloro-3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine

Product 1

HCID 118271755(R)-1-(3-(4-methoxybenzyl)-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-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine (30 mg, 0.054 mmol), (R)-1-(1-phenylethyl)urea (13.26 mg, 0.081 mmol), cesium carbonate (61.4 mg, 0.188 mmol) and BrettPhos pre-catalyst (4.8 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 to 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-(4-methoxybenzyl)-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 C44H40N6O2 [M+H]+ 685. found 685.

Workup

  1. customevacuated
  2. temperatureheated
  3. customreaction to 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-cbccc79b4a5141298d5da2d0024f4131
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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