Ammonium Chloride → HCID 67201062, compound

HRID 509973Notes

Reaction equation

HRID 509973 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[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:27]([O:31][C:32](=[O:52])[N:33]([CH2:42][C:43]1[C:44]([O:50][CH3:51])=[N:45][CH:46]=[C:47]([F:49])[CH:48]=1)[C:34]1[N:39]=[CH:38][C:37]([CH:40]=[O:41])=[CH:36][N:35]=1)([CH3:30])([CH3:29])[CH3:28].[Cl-].[NH4+]>O1CCCC1>[C:27]([O:31][C:32](=[O:52])[N:33]([C:34]1[N:39]=[CH:38][C:37]([CH:40]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[C:17]([O:19][CH3:20])[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:41])=[CH:36][N:35]=1)[CH2:42][C:43]1[C:44]([O:50][CH3:51])=[N:45][CH:46]=[C:47]([F:49])[CH:48]=1)([CH3:30])([CH3:28])[CH3:29]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 57963062HCID 57963062, compoundHCID 591287071-(Benzenesulfonyl)-3-iodo-5-methoxy-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 67201062HCID 67201062, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 1-benzenesulfonyl-3-iodo-5-methoxy-1H-pyrrolo[2,3-b]pyridine (16, 1 equivalent) in 4.0 mL of tetrahydrofuran, isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 1 equivalent) is added slowly at −50° C. The reaction is allowed to warm to 5° C. over 70 minutes, then cooled to −45° C. and (5-fluoro-2-methoxy-pyridin-3-ylmethyl)-(5-formyl-pyrimidin-2-yl)-carbamic acid tert-butyl ester (123, 0.78 equivalent) in 2.0 mL of tetrahydrofuran is added. The reaction is allowed to warm to room temperature over 1 hour, then poured into aqueous ammonium chloride and extracted with ethyl ether. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound.

Workup

  1. temperaturecooled to −45° C.
  2. temperatureto warm to room temperature over 1 hour
  3. extractionextracted with ethyl ether
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material is purified by silica gel column chromatography
  8. washeluting with 20-100% ethyl acetate in hexane
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-8652c57d4c984a7b93f59de11fd83022
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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