Cesium carbonate → (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea

HRID 590839Notes

Reaction equation

HRID 590839 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.[OH:42][C:43]([CH3:56])([CH3:55])[C@@H:44]([NH:51][C:52]([NH2:54])=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=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>[OH:42][C:43]([CH3:56])([CH3:55])[C@@H:44]([NH:51][C:52]([NH:54][C:2]1[CH:11]=[C:10]2[N:12]([C:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=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)=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 92170521(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)ureaHCID 1182723927-Chloro-3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine

Product 1

HCID 118381006(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)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 (40 mg, 0.072 mmol), (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)urea (22.4 mg, 0.108 mmol), cesium carbonate (82 mg, 0.25 mmol) and BrettPhos pre-catalyst (6.5 mg, 7.18 μM) 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 30 minutes. 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 (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea. MS ESI calc'd. for C46H44N6O3 [M+H]+ 729. found 729.

Workup

  1. customevacuated
  2. temperatureheated
  3. customreaction to 100° C. for 30 minutes
  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-6d14045d557545879379f0559d7dbf05
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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