Potassium Phosphate, Tribasic → HCID 71767098, compound

HRID 516972Notes

Reaction equation

HRID 516972 reaction equation
Cl[C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:22])[CH:8]=2)[N:3]=1.Cl.[O:24]1[CH2:29][CH2:28][N:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=2)[CH2:26][CH2:25]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.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>[Cl:22][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:27]3[CH2:28][CH2:29][O:24][CH2:25][CH2:26]3)=[CH:36][CH:35]=1)[CH:11]=[C:10]2[C:12]([NH:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:13]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 54594099(4-(MorpholinoMethyl)phenyl)boronic acid (hydrochloride)HCID 89855301HCID 89855301, compound

Product 1

HCID 71767098HCID 71767098, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

In a sealed 5 ml microwave vial, a suspension of 2,6-dichloro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 9) (158 mg, 0.47 mmol), [4-(morpholinomethyl)phenyl]boronic acid hydrochloride (240 mg, 0.93 mmol), potassium phosphate (198 mg, 0.93 mmol) and tetrakis(triphenylphosphine)palladium (0) (16 mg, 0.01 mmol) in DMF/Water 3/1 (4 ml) was heated at 130° C. under microwave irradiation for 30 minutes. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (50 ml) and washed with NaHCO3 saturated aqueous solution (25 ml). The organic layer was separated and dried over MgSO4 before concentration to dryness under reduced pressured. The reaction crude was purified by flash column chromatography using a 12 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 2 min hold 100% A followed by a 18 min ramp to 10% B and then 5 min hold at 10% B. The desired fractions were pooled together and concentrated to dryness under vacuum to obtain the crude material as an off-white solid (100 mg). The product was further purified by mass directed autopreparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired material as a white solid (68 mg, 0.14 mmol, Yield 30%).

Workup

  1. filtrationThe reaction was filtered through Celite™ and solvents
  2. customwere removed under reduced pressure
  3. washwashed with NaHCO3 saturated aqueous solution (25 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4 before concentration to dryness under reduced pressured
  6. customThe reaction crude
  7. customwas purified by flash column chromatography
  8. washeluting with DCM (Solvent A) and MeOH (Solvent B)
  9. custom2 min
  10. custom5 min
  11. concentrationconcentrated to dryness under vacuum
  12. customto obtain the crude material as an off-white solid (100 mg)
  13. customThe product was further purified by mass
  14. additionThe fractions containing product
  15. customfreeze dried

Sources & evidence

ORD record
ord-ecc9b10d1c134670ace04e966a6a5995
Source dataset
uspto-grants-2015_08
Patent number
US09115088B2

Reaction notes

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