Sodium Carbonate → HCID 46231381, compound

HRID 2246783Notes

Reaction equation

HRID 2246783 reaction equation
[C:1]([C:3]1([NH:6][C:7](=[O:35])[C@H:8]([CH2:30][C:31]([F:34])([CH3:33])[CH3:32])[NH:9][C@@H:10]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)[C:11]([F:14])([F:13])[F:12])[CH2:5][CH2:4]1)#[N:2].Cl[C:37]1[N:42]=[CH:41][C:40]([C:43]2([C:46]([NH2:48])=[O:47])[CH2:45][CH2:44]2)=[CH:39][CH:38]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C.C(O)CC>[NH2:48][C:46]([C:43]1([C:40]2[CH:39]=[CH:38][C:37]([C:18]3[CH:17]=[CH:16][C:15]([C@H:10]([NH:9][C@H:8]([C:7]([NH:6][C:3]4([C:1]#[N:2])[CH2:4][CH2:5]4)=[O:35])[CH2:30][C:31]([F:34])([CH3:33])[CH3:32])[C:11]([F:13])([F:12])[F:14])=[CH:20][CH:19]=3)=[N:42][CH:41]=2)[CH2:45][CH2:44]1)=[O:47]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 59767791(2S)-N-(1-Cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]amino]pentanamideHCID 717432671-(6-Chloro-3-pyridinyl)cyclopropanecarboxamide

Product 1

HCID 46231381HCID 46231381, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86598119Dimethylformamide n-propanolSolvent

Conditions

Temperature
80 °C

Procedure

A stream of nitrogen was passed through a solution of DMF/1-propanol (1 mL, 4 mL respectively), N1-(1-cyanocyclopropyl)-4-fluoro-N2-{(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-L-leucinamide from Example 1, Step 15, (150 mg), 1-(6-chloropyridin-3-yl)cyclopropanecarboxamide from Step 5 (74 mg) and 2 M Na2CO3 (400 μL) for 15 minutes followed by the addition of palladium acetate (II), complex (4:1) with triphenylphosphine (16 mg). The mixture was warmed to 80° C. for 8 hours under nitrogen. The mixture was cooled to room temperature, poured into ice (20 g) and saturated aqueous sodium bicarbonate (20 mL) and extracted with ethyl acetate (3×60 mL). The combined extracts were washed with brine and dried with magnesium sulfate. Removal of the solvent left a residue that was purified by chromatography on SiO2 (Combiflash) using ethyl acetate and hexanes (60% for 10 minutes, then 60 to 100% for 30 minutes) as eluants, followed by a swish using diethyl ether and hexanes to yield the title compound.

Workup

  1. customfor 15 minutes
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate (3×60 mL)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried with magnesium sulfate
  6. customRemoval of the solvent
  7. waitleft a residue that
  8. customwas purified by chromatography on SiO2 (Combiflash)
  9. customfor 10 minutes

Sources & evidence

ORD record
ord-c673c64083a84daeb21e5784c6eb9811
Source dataset
uspto-grants-2010_03
Patent number
US07687524B2

Reaction notes

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