Ammonium Chloride → 5-[(1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-hydroxy-methyl]-pyridin-2-yl-(2-fluoro-benzyl)-carbamic acid tert-butyl ester

HRID 1024272Notes

Reaction equation

HRID 1024272 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12](I)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:49])[N:32]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[F:48])[C:33]1[CH:38]=[CH:37][C:36]([CH:39]=[O:40])=[CH:35][N:34]=1)([CH3:29])([CH3:28])[CH3:27].[Cl-].[NH4+]>O1CCCC1>[C:26]([O:30][C:31](=[O:49])[N:32]([C:33]1[CH:38]=[CH:37][C:36]([CH:39]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=3)[N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH:11]=2)[OH:40])=[CH:35][N:34]=1)[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[F:48])([CH3:29])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 242292391-Benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridineHCID 57619276(2-Fluoro-benzyl)-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl esterHCID 178418918HCID 178418918, compound

Product 1

HCID 576191885-[(1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-hydroxy-methyl]-pyridin-2-yl-(2-fluoro-benzyl)-carbamic acid tert-butyl esterYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 1-benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine (581, 0.420 g, 1.00 mmol) in tetrahydrofuran (15.0 mL) at −40° C. under nitrogen, isopropylmagnesium chloride (2.0M in tetrahydrofuran, 0.49 mL) was added slowly. The reaction was allowed to warm to 5° C. over 70 minutes, then cooled to −40° C., followed by adding (2-fluoro-benzyl)-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester 579 in tetrahydrofuran (6.0 mL). The reaction was allowed to warm to room temperature over 1 hour, then poured into aqueous ammonium chloride, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (582, 0.25 g, 41%). MS (ESI) [M+H+]=623.1.

Workup

  1. temperaturecooled to −40° C.
  2. temperatureto warm to room temperature over 1 hour
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 20% to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f804cb618c9e41cf8c1b7cb0291ba09c
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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