Sodium Carbonate → HCID 118308077, compound

HRID 1750677Notes

Reaction equation

HRID 1750677 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C@H:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N:22]2[N:26]=[CH:25][CH:24]=[N:23]2)=[N:6][CH:7]=1.ClC1N=CC(N[C@H]2CCC[C@@H]2N[C:42](=O)[C:43]2[CH:48]=CC=CC=2N2N=CC=N2)=NC=1.C1(B(O)O)CC1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:48]1([C:2]2[N:3]=[CH:4][C:5]([NH:8][C@H:9]3[CH2:13][CH2:12][CH2:11][C@@H:10]3[NH:14][C:15](=[O:27])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[N:22]3[N:26]=[CH:25][CH:24]=[N:23]3)=[N:6][CH:7]=2)[CH2:43][CH2:42]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acid2×HCID 118308312HCID 118308312, compoundHCID 118308320HCID 118308320, compound

Product 1

HCID 118308077HCID 118308077, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-[(1S,2S)-2-[(5-bromopyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide and N-[(1S,2S)-2-[(5-chloropyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 30a and 30b; 100 mg, 0.23 mmol), cyclopropylboronic acid (CAS number 411235-57-9; 60 mg, 0.70 mmol), sodium carbonate (aq. 2 M, 350 μl, 0.70 mmol) and tetrakis(triphenylphosphine)palladium (27 mg, 0.023 mmol) in 1,4-dioxane (778 μl) was sealed, purged and evacuated with nitrogen and then subjected to microwave irradiation at 100° C. for 1 hour. To this was then added further cyclopropylboronic acid (CAS number 411235-57-9; 60 mg, 0.70 mmol) and tetrakis(triphenylphosphine)palladium (27 mg, 0.023 mmol). The reaction was sealed, purged and evacuated with nitrogen and again subjected to microwave irradiation at 140° C. for 20 minutes. The reaction was partitioned between ethyl acetate and water, washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) and then purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% formic acid) and further purified by column chromatography (basic silica, 0-100% ethyl acetate/petrol) to afford the title compound.

Workup

  1. customwas sealed
  2. custompurged
  3. customevacuated with nitrogen
  4. customirradiation at 100° C. for 1 hour
  5. customThe reaction was sealed
  6. custompurged
  7. customevacuated with nitrogen
  8. customirradiation at 140° C. for 20 minutes
  9. customThe reaction was partitioned between ethyl acetate and water
  10. washwashed with water, brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated in vacuo
  13. customThe resulting residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol)
  14. custompurified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% formic acid)
  15. customfurther purified by column chromatography (basic silica, 0-100% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-631df34012b14473a406386f76203d98
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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