3-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine → HCID 57619424, compound

HRID 1024226Notes

Reaction equation

HRID 1024226 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:48])[N:32]([C:40]1[S:41][C:42]([CH:46]=[O:47])=[C:43]([Cl:45])[N:44]=1)[CH2:33][C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1)([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[C:26]([O:30][C:31](=[O:48])[N:32]([C:40]1[S:41][C:42]([CH:46]([OH:47])[C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[C:43]([Cl:45])[N:44]=1)[CH2:33][C:34]1[CH:35]=[CH:36][N:37]=[CH:38][CH:39]=1)([CH3:29])([CH3:27])[CH3:28]

Participants

5

Reactant 3

HCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 57619296HCID 57619296, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57619424HCID 57619424, compoundYield 86.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (96, 0.44 g, 1.1 mmol) in tetrahydrofuran (20 mL) at −20° C., isopropylmagnesium chloride (2M in tetrahydrofuran, 0.6 mL, 1.2 mmol) was added dropwise. The reaction mixture was allowed to warm to 0° C. in 10 minutes. The reaction mixture was then cooled to −40° C. A solution of (4-chloro-5-formyl-thiazol-2-yl)-pyridin-4-ylmethyl-carbamic acid tert-butyl ester (518, 0.26 g, 0.73 mmol) in tetrahydrofuran (4 mL) was added to the reaction mixture. The reaction mixture was allowed to warm to −10° C. over 30 minutes. The reaction mixture was poured into ice water, extracted with ethyl acetate, washed with brine, and dried over sodium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexanes to provide the desired compound as a yellow solid (519, 397 mg, 86%). MS (ESI) [M+H+]+=628.3.

Workup

  1. temperatureThe reaction mixture was then cooled to −40° C
  2. temperatureto warm to −10° C. over 30 minutes
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. customAfter removal of solvent
  7. customthe residue was purified by silica gel column chromatography
  8. washeluting with ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f9676c756c3d4fd0adf636d3bef3f5d5
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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