(5-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzoimidazol-2-ylmethoxy)-phenyl]-methanol → 6-Chloro-2-[5-fluoro-2-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-phenoxymethyl]-1H-benzimidazole

HRID 253467Notes

Reaction equation

HRID 253467 reaction equation
ClC1C=C2C(C(C3C=C(OC)C(OCC4N(C)C5C=CC=CC=5N=4)=CC=3F)O)=CN([Si](C(C)C)(C(C)C)C(C)C)C2=NC=1.C(OC([N:51]1[C:55]2[CH:56]=[CH:57][C:58]([Cl:60])=[CH:59][C:54]=2[N:53]=[C:52]1[CH2:61][O:62][C:63]1[CH:68]=[C:67]([F:69])[C:66]([CH:70](O)[C:71]2[C:79]3[C:74](=[N:75][CH:76]=[CH:77][CH:78]=3)[N:73]([Si](C(C)C)(C(C)C)C(C)C)[CH:72]=2)=[CH:65][C:64]=1[O:91][CH3:92])=O)(C)(C)C>>[Cl:60][C:58]1[CH:57]=[CH:56][C:55]2[N:51]=[C:52]([CH2:61][O:62][C:63]3[CH:68]=[C:67]([F:69])[C:66]([CH2:70][C:71]4[C:79]5[C:74](=[N:75][CH:76]=[CH:77][CH:78]=5)[NH:73][CH:72]=4)=[CH:65][C:64]=3[O:91][CH3:92])[NH:53][C:54]=2[CH:59]=1

Participants

3

Reactant 2

HCID 66888056(5-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzoimidazol-2-ylmethoxy)-phenyl]-methanolHCID 668894835-Chloro-2-{5-fluoro-4-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-2-methoxy-phenoxymethyl}-benzimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 249566486-Chloro-2-[5-fluoro-2-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-phenoxymethyl]-1H-benzimidazoleYield 59%

Procedure

6-Chloro-2-[5-fluoro-2-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-phenoxymethyl]-1H-benzimidazole (P-2112) was prepared using the same protocol as described in Scheme 47, step 4, substituting (5-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzoimidazol-2-ylmethoxy)-phenyl]-methanol 145 with (5-chloro-2-{5-fluoro-4-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-2-methoxy-phenoxymethyl}-benzoimidazole-1-carboxylic acid tert-butyl ester 153. Purification with silica gel flash chromatography eluting with a gradient of methanol (2 to 25%) in dichloromethane gave the desired compound (P-2112, 0.052 g, 59%). MS (ESI) [M+H+]+=437.1, 439.1.

Workup

  1. custom6-Chloro-2-[5-fluoro-2-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-phenoxymethyl]-1H-benzimidazole (P-2112) was prepared
  2. customPurification with silica gel flash chromatography
  3. washeluting with a gradient of methanol (2 to 25%) in dichloromethane

Sources & evidence

ORD record
ord-f908c9f926644c709c3bbce8a3dd99bc
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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