Tetrahydrofuran → 7-Chloro-3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine

HRID 590842Notes

Reaction equation

[CH2:1]([NH:8][CH:9]([CH3:41])[CH2:10][C:11]1[C:16]2[C:17](I)=[N:18][N:19](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:15]=2[CH:14]=[C:13]([Cl:40])[N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:43]([O-:46])(C)C.[Na+].C1COCC1>CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CCOC(C)=O>[Cl:40][C:13]1[CH:14]=[C:15]2[NH:19][N:18]=[C:17]3[C:16]2=[C:11]([CH2:10][CH:9]([CH3:41])[N:8]3[CH2:1][C:2]2[CH:7]=[CH:6][C:5]([O:46][CH3:43])=[CH:4][CH:3]=2)[N:12]=1

Participants

Conditions

Temperature: 55 °C

Procedure

N-benzyl-1-(6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)propan-2-amine (670 mg, 0.958 mmol) and RuPhos pre-catalyst (70 mg, 0.096 mmol) were charged in a 2 dram vial, evacuated and backfilled with nitrogen and taken in toluene (4.8 mL). A solution of 2M NaOtBu in THF (1.2 ml, 2.4 mmol) was added and the reaction mixture was heated to 55° C. for 12 hours. The reaction mixture was cooled and diluted with EtOAc and washed with water, brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-50% EtOAc-hexanes) gave 7-chloro-3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridine. MS ESI calc'd. for C35H30ClIN4 [M+H]+ 572. found 572.

Workup

customevacuated
temperatureThe reaction mixture was cooled
washwashed with water, brine
dry with materialdried with sodium sulfate
concentrationconcentrated
customPurification of the residue by flash column (0-50% EtOAc-hexanes)

Sources & evidence

ORD record: ord-12d977be2ac84c5e931e3c600dbe2d44
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233979B2

Reaction notes

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