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

HRID 1952129Notes

Reaction equation

HRID 1952129 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 was 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 was concentrated
  8. custompurified by silica gel column chromatography
  9. washeluting with 20% to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-72be127f93e2478490d4756f72607385
Source dataset
uspto-grants-2013_03
Patent number
US08404700B2

Reaction notes

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