Lithium Hexamethyldisilazide → 3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine

HRID 588166Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH3:31])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[Li+].C[Si]([N-:37][Si](C)(C)C)(C)C>C1COCC1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[Pd]>[CH3:31][O:30][C:8]1[C:5]2[CH:6]=[N:7][C:2]([NH2:37])=[CH:3][C:4]=2[N:10]([C:11]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:9]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Under inert atmosphere, to a solution of 6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine (0.4 g, 0.94 mmol, see Example 40/Step 1) in anhydrous THF (10 mL) was added SPHOS Pd precatalyst (0.07 g, 0.094 mmol) and LiHMDS (1.0 M solution in Toluene, 1.9 mL, 1.9 mmol) and the contents were heated at 70° C. After 5 h, the reaction mixture was brought back to ambient temperature and quenched with NH4Cl (5 mL). The organic contents were then extracted with EtOAc and the volatiles were then removed under reduced pressure. The residue thus obtained was purified by a flash column chromatography to afford the title compound. H1NMR (CDCl3, 400 MHz): δ 8.38 (s, 1H), 7.29-7.26 (m, 15H), 5.03 (s, 1H), 4.50 (bs, 2H), 3.93 (s, 3H).

Workup

customwas brought back to ambient temperature
customquenched with NH4Cl (5 mL)
extractionThe organic contents were then extracted with EtOAc
customthe volatiles were then removed under reduced pressure
customThe residue thus obtained
customwas purified by a flash column chromatography

Sources & evidence

ORD record: ord-eb3b4add3f8143cca278d116999bae26
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09226922B2

Reaction notes

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