Ammonium Chloride → [2,6-difluoro-3-(propane-1-sulfonylamino)-benzyl]-5-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl-carbamic acid tert-butyl ester

HRID 1367380Notes

Reaction equation

HRID 1367380 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.[C:26]([O:30][C:31](=[O:57])[N:32]([CH2:41][C:42]1[C:47]([F:48])=[CH:46][CH:45]=[C:44]([NH:49][S:50]([CH2:53][CH2:54][CH3:55])(=[O:52])=[O:51])[C:43]=1[F:56])[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:57])[N:32]([CH2:41][C:42]1[C:47]([F:48])=[CH:46][CH:45]=[C:44]([NH:49][S:50]([CH2:53][CH2:54][CH3:55])(=[O:52])=[O:51])[C:43]=1[F:56])[C:33]1[CH:38]=[CH:37][C:36]([CH:39]([OH:40])[C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[CH:35][N:34]=1)([CH3:28])([CH3:27])[CH3:29]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 57619377[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzyl]-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl esterHCID 178418918HCID 178418918, compound

Product 1

HCID 57619431[2,6-difluoro-3-(propane-1-sulfonylamino)-benzyl]-5-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
15 °C

Procedure

To a solution of 3-Iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (96, 0.644 g, 1.61 mmol) in tetrahydrofuran (10.0 mL) at −40° C. under nitrogen, isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 0.80 mL) was added slowly. The reaction was allowed to warm to 15° C. over 100 minutes, then cooled to −40° C., followed by adding [2,6-difluoro-3-(propane-1-sulfonylamino)-benzyl]-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (560, 0.100 g, 0.21 mmol, prepared as described in Example 60, Scheme 175) in tetrahydrofuran (2.0 mL). The reaction was allowed to warm to 5° C. over 2 hours, 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 a yellow solid (574, 75 mg, 47%). MS (ESI) [M+H+]+=744.7.

Workup

  1. temperaturecooled to −40° C.
  2. temperatureto warm to 5° C. over 2 hours
  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
  9. customto give a yellow solid (574, 75 mg, 47%)

Sources & evidence

ORD record
ord-48f2291e980a473ba72b2d3e75366ce9
Source dataset
uspto-grants-2011_02
Patent number
US07893075B2

Reaction notes

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