Ammonium Chloride → 1-(2-Fluoro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

HRID 1367384Notes

Reaction equation

HRID 1367384 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si](C(C)C)(C(C)C)C(C)C)[CH:3]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:49])[N:32](CC1C=CC=CC=1F)[C:33]1[CH:38]=[CH:37][C:36]([CH:39]=[O:40])=[CH:35][N:34]=1)([CH3:29])([CH3:28])[CH3:27].[F:50][C:51]1[CH:58]=[CH:57][CH:56]=[CH:55][C:52]=1[CH:53]=O.[Cl-].[NH4+]>O1CCCC1>[C:26]([O:30][C:31](=[O:49])[NH:32][CH:33]1[CH:38]=[CH:37][C:36]([C:39]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[NH:4][CH:3]=2)=[O:40])=[CH:35][N:34]1[CH2:53][C:52]1[CH:55]=[CH:56][CH:57]=[CH:58][C:51]=1[F:50])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 67970o-FluorobenzaldehydeHCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-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 690750571-(2-Fluoro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-pyridin-2-yl]-carbamic acid tert-butyl esterYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To 3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (96, 0.550 g, 1.37 mmol) in tetrahydrofuran (15.0 mL) at −40° C. under nitrogen, isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 0.65 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, prepared according to the protocol of Example 17, Scheme 19, Steps 1-3, replacing 4-chlorobenzaldehyde 40 with 2-fluoro-benzaldehyde in Step 1) in tetrahydrofuran (4.0 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 w as concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (580, 0.14 g, 26%). MS (ESI) [M+H+]+=447.0.

Workup

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

Sources & evidence

ORD record
ord-181440775a564a64bf750259c2c0baa9
Source dataset
uspto-grants-2011_02
Patent number
US07893075B2

Reaction notes

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