Ammonium Chloride → HCID 52933299, compound

HRID 510015Notes

Reaction equation

HRID 510015 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([O:11][CH3:12])[CH:9]=2)[N:4]([Si](C(C)C)(C(C)C)C(C)C)[CH:3]=1.C([Mg]Cl)(C)C.C(OC(=O)[N:34]([CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[Cl:51])[C:35]1[CH:40]=[CH:39][C:38]([CH:41]=O)=[C:37]([F:43])[N:36]=1)(C)(C)C.[Cl-].[NH4+]>O1CCCC1>[Cl:51][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=1[CH2:44][NH:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([O:11][CH3:12])[CH:9]=3)[NH:4][CH:3]=2)=[C:37]([F:43])[N:36]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 57963111HCID 57963111, compoundHCID 58259088HCID 58259088, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 52933299HCID 52933299, compoundYield 160%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To 3-iodo-5-methoxy-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (5, 0.49 g, 1.14 mmol) in 6.8 mL of tetrahydrofuran at −50° C. under nitrogen, isopropylmagnesium chloride (0.569 mL, 2.0 M in tetrahydrofuran, 1.14 mmol) was added slowly. The reaction was allowed to warm to 5° C. over 70 minutes, then cooled to −60° C. and (2-chloro-benzyl)-(6-fluoro-5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (48, 0.23 g, 0.63 mmol) in 30.0 mL of tetrahydrofuran was added. 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 sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound as a white solid (176, 0.400 g). MS (ESI) [M+H+]+=669.4.

Workup

  1. temperaturecooled to −60° C.
  2. temperatureto warm to room temperature over 1 hour
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material was purified by silica gel column chromatography
  8. washeluting with 20-100% ethyl acetate in hexane
  9. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-ee7553f4d902439fa212ceae47cbce87
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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