HCID 57619217, compound → HCID 57619456, compound

HRID 1024307Notes

Reaction equation

HRID 1024307 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:5]2=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[C:27]([O:31][C:32](=[O:50])[N:33]([CH2:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1)[C:34]1[S:35][C:36]([CH:40]=[O:41])=[C:37](Cl)[N:38]=1)([CH3:30])([CH3:29])[CH3:28]>O1CCCC1>[C:27]([O:31][C:32](=[O:50])[N:33]([C:34]1[S:35][C:36]([CH:40]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[N:8]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:9]=2)[OH:41])=[CH:37][N:38]=1)[CH2:42][C:43]1[CH:44]=[CH:45][C:46]([F:49])=[CH:47][CH:48]=1)([CH3:30])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 57619217HCID 57619217, compoundHCID 580879285-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 57619456HCID 57619456, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (626, 300 mg, 0.69 mmol) in tetrahydrofuran (10 mL) at −20° C. was added dropwise iso-propyl-magnesium chloride (2M in tetrahydrofuran, 0.44 mL, 0.88 mmol). The reaction mixture was allowed to warm to 0° C. over 10 minutes and then cooled to −40° C. To this reaction mixture was added a solution of (4-fluoro-benzyl)-(4-chloro-5-formyl-thiazol-2-yl)-carbamic acid tert-butyl ester (625, 211 mg, 0.63 mmol) in tetrahydrofuran (5 mL). The reaction mixture was allowed to warm to 0° C. over 30 minutes and then quenched with brine (50 mL). The mixture was transferred to a separatory funnel and the layers were separated. The organic layer was dried over sodium sulfate and evaporated in vacuo to give the crude material which was purified by silica gel column chromatography (0-30% ethyl acetate/heptane) to provide the desired compound as a foam (120 mg, 30%), consistent with structure by 1H-NMR.

Workup

  1. temperaturecooled to −40° C
  2. temperatureto warm to 0° C. over 30 minutes
  3. customquenched with brine (50 mL)
  4. customThe mixture was transferred to a separatory funnel
  5. customthe layers were separated
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customevaporated in vacuo
  8. customto give the crude material which
  9. customwas purified by silica gel column chromatography (0-30% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-f2b25060e7f34a52849d61622501a137
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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