3-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine → [5-(4-chloro-benzyloxy)-4-methoxy-pyridin-2-yl]-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

HRID 253410Notes

Reaction equation

HRID 253410 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.[Cl:26][C:27]1[CH:44]=[CH:43][C:30]([CH2:31][O:32][C:33]2[C:34]([O:41][CH3:42])=[CH:35][C:36]([CH:39]=[O:40])=[N:37][CH:38]=2)=[CH:29][CH:28]=1>O1CCCC1>[Cl:26][C:27]1[CH:44]=[CH:43][C:30]([CH2:31][O:32][C:33]2[C:34]([O:41][CH3:42])=[CH:35][C:36]([CH:39]([C:2]3[C:10]4[C:5](=[N:6][CH:7]=[CH:8][CH:9]=4)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=3)[OH:40])=[N:37][CH:38]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 580874295-(4-Chloro-benzyloxy)-4-methoxy-pyridine-2-carbaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 58087829[5-(4-chloro-benzyloxy)-4-methoxy-pyridin-2-yl]-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanolYield 59.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

3-Iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (68, 180 mg, 0.450 mmol, prepared as described in Example 22) was dissolved in tetrahydrofuran (2.5 mL) and the reaction was cooled to −20° C. under an atmosphere of nitrogen. Isopropylmagnesium chloride in tetrahydrofuran (2.00 M, 0.243 mL) was added. The reaction was stirred for 1 hour, during which the temperature rose to 0° C. The reaction was cooled to −20° C. and 5-(4-chloro-benzyloxy)-4-methoxy-pyridine-2-carbaldehyde (74, 80.0 mg, 0.288 mmol) in tetrahydrofuran (0.75 mL) was added. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was quenched with methanol and adsorbed onto silica, then purified by silica gel chromatography, methanol:dichloromethane, to provide the desired compound (75, 94 mg, 59%). 1H-NMR was consistent with the desired compound. MS (ESI) [M+H+]+=552.4, 554.4, 555.4.

Workup

  1. customrose to 0° C
  2. temperatureThe reaction was cooled to −20° C.
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. customThe reaction was quenched with methanol
  6. custompurified by silica gel chromatography, methanol

Sources & evidence

ORD record
ord-b3cb8032d4eb4b94a2091f5296ed157f
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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