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

HRID 590843Notes

Reaction equation

Cl[C:2]1[CH:11]=[C:10]2[NH:12][N:13]=[C:8]3[C:9]2=[C:4]([CH2:5][CH:6]([CH3:23])[N:7]3[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[N:3]=1.[C:24]1([C@H:30]([NH:32][C:33]([NH2:35])=[O:34])[CH3:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=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>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:7]2[CH:6]([CH3:23])[CH2:5][C:4]3[N:3]=[C:2]([NH:35][C:33]([NH:32][C@@H:30]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH3:31])=[O:34])[CH:11]=[C:10]4[NH:12][N:13]=[C:8]2[C:9]=34)=[CH:16][CH:17]=1

Participants

Conditions

Temperature: 100 °C

Procedure

7-chloro-3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine (150 mg, 0.263 mmol), (R)-1-(1-phenylethyl)urea (64.7 mg, 0.394 mmol), cesium carbonate (257 mg, 0.788 mmol) and BrettPhos pre-catalyst (23.8 mg, 0.026 mmol) were charged in a 1 dram vial, evacuated and backfilled with nitrogen and taken in 1,4-dioxane (1.4 mL). The mixture was heated at 100° C. for 1 hour before it was diluted with DCM, washed with water, brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-80% EtOAc-hexanes) gave 1-(3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea. MS ESI calc'd. for C26H28N6O2[M+H]+ 699. found 699.

Workup

customevacuated
additionwas diluted with DCM
washwashed with water, brine
dry with materialdried with sodium sulfate
concentrationconcentrated
customPurification of the residue by flash column (0-80% EtOAc-hexanes)

Sources & evidence

ORD record: ord-1cb5e1c1b9a2405289a5819325a6a32b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233979B2

Reaction notes

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