Ammonia → HCID 58259261, compound

HRID 509988Notes

Reaction equation

HRID 509988 reaction equation
[C:1]([O:5][C:6](=[O:24])[N:7]([C:16]1[CH:21]=[CH:20][C:19](Br)=[C:18]([F:23])[N:17]=1)[CH2:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:15])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.[C:30]([O:34][C:35]([N:37]1[C:41]2=[N:42][CH:43]=[C:44]([Cl:46])[CH:45]=[C:40]2[C:39]([CH2:47]Cl)=[CH:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].N>O1CCCC1>[C:30]([O:34][C:35]([N:37]1[C:41]2=[N:42][CH:43]=[C:44]([Cl:46])[CH:45]=[C:40]2[C:39]([CH2:47][C:19]2[C:18]([F:23])=[N:17][C:16]([N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:24])[CH2:8][C:9]3[CH:10]=[N:11][CH:12]=[C:13]([F:15])[CH:14]=3)=[CH:21][CH:20]=2)=[CH:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 57619177HCID 57619177, compoundHCID 57619241HCID 57619241, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 58259261HCID 58259261, compoundYield 22.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-35 °C

Procedure

To (5-bromo-6-fluoro-pyridin-2-yl)-(5-fluoro-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (143, 0.600 g, 1.50 mmol) in 10.0 mL of tetrahydrofuran at −25° C. under nitrogen, isopropylmagnesium chloride (0.730 mL, 2.0 M in tetrahydrofuran, 1.46 mmol) was added and the reaction allowed to come to 5° C. over 1 hour. The reaction was then cooled to −35° C., and CuCN-2LiCl (2.0 mL, 0.75 M in tetrahydrofuran, 1.5 mmol) was added. After 5 minutes, 5-chloro-3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (142, 0.300 g, 0.996 mmol) in 4.0 mL of tetrahydrofuran was added and the reaction allowed to come to room temperature over 1 hour. The reaction was poured into dilute ammonia solution and extracted with ethyl acetate. The organic layer was separated, 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 solvent removed under vacuum to provide the desired compound (144, 130 mg). MS (ESI) [M+H]+=586.2.

Workup

  1. waitAfter 5 minutes
  2. waitto come to room temperature over 1 hour
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with 20-100% ethyl acetate in hexane
  10. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-88feebb8c8ac4f05b7880718630cadc0
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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