Methyl iodide → HCID 59024141, compound

HRID 1678265Notes

Reaction equation

HRID 1678265 reaction equation
[S:1]1[C:5]([C:6]2[C:14]3[C:10](=[CH:11][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:13]=3)[CH:9]=[C:8]([Br:23])[CH:7]=2)=[CH:4][C:3]2[CH:24]=[CH:25][CH:26]=[CH:27][C:2]1=2.[CH2:28]([Li])CCC.CI.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.O>[S:1]1[C:5]([C:6]2[C:14]3[C:10](=[C:11]([CH3:28])[N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:20])[CH3:21])[N:13]=3)[CH:9]=[C:8]([Br:23])[CH:7]=2)=[CH:4][C:3]2[CH:24]=[CH:25][CH:26]=[CH:27][C:2]1=2

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 59023903HCID 59023903, compoundHCID 178418339Butyllithium

Product 1

HCID 59024141HCID 59024141, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-65 °C

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.

Workup

  1. temperaturethe solution was warmed to about −20° C
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-2eb74771d8e5495480de6c5faea9fc9b
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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