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

HRID 253459Notes

Reaction equation

HRID 253459 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:34]=[C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=2[F:44])[C:32]([O:45][CH3:46])=[CH:31][C:28]=1[CH:29]=[O:30]>O1CCCC1>[Cl:26][C:27]1[CH:34]=[C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=2[F:44])[C:32]([O:45][CH3:46])=[CH:31][C:28]=1[CH:29]([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)[OH:30]

Participants

5

Reactant 3

HCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 598038352-Chloro-4-(4-chloro-2-fluoro-benzyloxy)-5-methoxy-benzaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 59803877[2-chloro-4-(4-chloro-2-fluoro-benzyloxy)-5-methoxy-phenyl]-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanolYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (68, 582.0 mg, 1.45 mmol, prepared as described in Example 22) was dissolved in tetrahydrofuran (10.0 mL) at −20° C. under an atmosphere of nitrogen. Isopropylmagnesium chloride in tetrahydrofuran (2.0 M, 0.79 mL) was added to the reaction. The reaction was stirred for 1 hour, during which the temperature rose to 0° C. The reaction was cooled to −20° C. and 2-chloro-4-(4-chloro-2-fluoro-benzyloxy)-5-methoxy-benzaldehyde (140, 200 mg, 0.61 mmol) in tetrahydrofuran (7.0 mL) was added. The reaction was stirred for 1.5 hours during which time the temperature rose to 0° C. The reaction was quenched with methanol and adsorbed onto silica, then purified by silica gel chromatography, eluting with 0-20% ethyl acetate:hexanes, to provide the desired compound (141, 318 mg, 87%). MS (ESI): [M+H+]+=603.3, 605.3.

Workup

  1. customrose to 0° C
  2. stirringThe reaction was stirred for 1.5 hours during which time the temperature
  3. customrose to 0° C
  4. customThe reaction was quenched with methanol
  5. custompurified by silica gel chromatography
  6. washeluting with 0-20% ethyl acetate

Sources & evidence

ORD record
ord-22f8ed3831154667a5aefa787fd6fec7
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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