HCID 59024184, compound → HCID 178434207, compound

HRID 1678266Notes

Reaction equation

[S:1]1[C:5]([C:6]2[C:14]3[C:10](=[C:11]([CH3:23])[N:12](COCC[Si](C)(C)C)[N:13]=3)[CH:9]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:7]=2)=[CH:4][C:3]2[CH:33]=[CH:34][CH:35]=[CH:36][C:2]1=2.B([O-])[O-].C(OC([N:47]1[C:55]2[CH:54]=[N:53][C:52]([N:56]=CN(C)C)=[N:51][C:50]=2[C:49](I)=[CH:48]1)=O)(C)(C)C>>[S:1]1[C:5]([C:6]2[CH:7]=[C:8]([C:49]3[C:50]4[N:51]=[C:52]([NH2:56])[N:53]=[CH:54][C:55]=4[NH:47][CH:48]=3)[CH:9]=[C:10]3[C:14]=2[NH:13][N:12]=[C:11]3[CH3:23])=[CH:4][C:3]2[CH:33]=[CH:34][CH:35]=[CH:36][C:2]1=2

Participants

Reactant 3

HCID 59024184HCID 59024184, compound

HCID 66791406HCID 66791406, compound

HCID 178514824HCID 178514824, compound

Product 1

HCID 178434207HCID 178434207, compoundYield 19%

Procedure

A mixture of 7-benzo[b]thiopen-2-yl-5-bromo-2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazole (Preparation #24, 1.0 g, 2.18 mmol) in tetrahydrofuran (15 mL) was cooled to about −65° C. then a solution of n-butyllithium (1.6 M, 1.5 mL, 2.4 mmol) was added dropwise. After about 5 minutes methyliodide (0.37 g, 2.6 mmol) was added then the solution was warmed to about −20° C. Saturated ammonium chloride (1 mL) was added then the mixture was diluted with ethyl acetate (25 mL) and water (10 mL). The layers were separated then the organic layer was dried over magnesium sulfate, filtered and evaporated to give the crude 7-benzo[b]thiophen-2-yl-5-bromo-3-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazole which was converted to 7-benzo[b]thiophen-2-yl-3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazole (0.29 g, 25% over 2 steps) using general procedure E. The boronate (200 mg, 0.385 mmol) was coupled with 2-(dimethylamino-methyleneamino)-7-iodo-pyrrolo[3,2-d]pyrimidine-5-carboxylic acid tert-butyl ester (0.135 g, 0.32 mmol) using general procedure F and the resulting product deprotected using general procedure G to give 7-(7-benzo[b]thiophen-2-yl-3-methyl-1H-indazol-5-yl)-5H-pyrrolo[3,2-d]pyrimidin-2-ylamine (24 mg, 19%); (DMSO-d6, 400 MHz) δ 12.48 (bs, 1H), 11.44 (s, 1H), 8.50 (m, 3H), 8.18 (d, 1H), 8.07 (bs, 1H), 8.02 (d, 1H), 7.90 (d, 1H), 7.43 (m, 2H), 5.94 (bs, 2H), 2.61 (s, 3H); RP-HPLC (Table 1, Method e) Rt 1.76 min; m/z: (M−H)− 394.9.

Sources & evidence

ORD record: ord-2cbad85a70a940f1acabef9541b432e2
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08008481B2

Reaction notes

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