HCID 131735982, compound → HCID 117843297, compound

HRID 2209245Notes

Reaction equation

HRID 2209245 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]3[N:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O-:25])=[O:24])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[CH:8]=[C:7]([O:26][C@@H:27]([C@@H:29]3[CH2:33][C:32](=[O:34])[N:31]([C@@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=4)[CH3:36])[CH2:30]3)[CH3:28])[C:6]=12.[Br-].[CH:46]1([Zn+])[CH2:48][CH2:47]1>[Cl-].[NH4+]>[CH:46]1([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[C:9]([C:11]4[N:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][N:20]([C:23]([O:25][C:9]([CH3:11])([CH3:10])[CH3:8])=[O:24])[CH2:19][CH2:18]5)=[CH:13][CH:12]=4)[CH:8]=[C:7]([O:26][C@@H:27]([C@@H:29]4[CH2:33][C:32](=[O:34])[N:31]([C@@H:35]([C:37]5[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=5)[CH3:36])[CH2:30]4)[CH3:28])[C:6]=23)[CH2:48][CH2:47]1

Participants

4

Reactant 2

HCID 131735982HCID 131735982, compoundHCID 178419765HCID 178419765, compound

Product 1

HCID 117843297HCID 117843297, compound

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

To an appropriate sized microwave vial, 4-(6-(3-iodo-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)pyridin-3-yl)piperazine-1-carboxylate 6.48 (35 mg, 0.046 mmol) and [(2-dicyclohexylphosphino-2′,6′-bis(N,N-dimethylamino)-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate (3.7 mg, 0.0046 mmol) were added. After evacuating and backfilling with nitrogen, THF (1.0 mL) was added followed by cyclopropylzinc bromide (0.55 mL, 0.27 mmol, 0.5M solution in THF). The mixture was stirred at room temperature for 15 min. The reaction was diluted with a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to afford tert-butyl 4-(6-(3-cyclopropyl-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)pyridin-3-yl)piperazine-1-carboxylate 6.49.

Workup

  1. customAfter evacuating
  2. additionwas added
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-9d17432713244424b7b6bda7077316e9
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…