Potassium Phosphate, Tribasic → M-5717

HRID 516971Notes

Reaction equation

HRID 516971 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]([F: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>[F: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 89854159HCID 89854159, compound

Product 1

HCID 71748268M-5717

Reagents, catalysts & solvents 2

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

Procedure

In a sealed microwave tube, a suspension of 2-chloro-6-fluoro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 4) (2.00 g, 6 mmol), [4-(morpholinomethyl)phenyl]boronic acid, hydrochloride, available from UORSY, (3.20 g, 12 mmol), potassium phosphate (2.63 g, 12 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.21 g, 0.19 mmol) in DMF/Water 3/1 (40 ml) was heated at 130° C. under microwave irradiation for 30 min. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (150 ml) and washed twice with NaHCO3 saturated aqueous solution (2×100 ml). The organic layer was separated, dried over MgSO4 and concentrate to dryness under reduced pressure. The reaction crude was purified by flash column chromatography using an 80 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 1 min hold 100% A, followed by a 30 min ramp to 10% B, and then 15 min hold at 10% B. The fractions containing product were pooled together and concentrated to dryness under vacuum to obtain the desired product as an off-white solid (1 g). The product was dissolved in methanol (100 ml) and 3-mercaptopropyl ethyl sulfide Silica (Phosphonics, SPM-32, 60-200 uM) was added. The suspension was stirred at room temperature over for 2 days and then at 50° C. for 1 h. After cooling to room temperature, the scavenger was filtered off and washed with methanol (30 ml). The solvent was removed under reduced pressure and the product was further purified by preparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired product as a white solid (0.6 g, 1.3 mmol, Yield 20%).

Workup

  1. filtrationThe reaction was filtered through Celite™ and solvents
  2. customwere removed under reduced pressure
  3. washwashed twice with NaHCO3 saturated aqueous solution (2×100 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrate to dryness under reduced pressure
  7. customThe reaction crude
  8. customwas purified by flash column chromatography
  9. washeluting with DCM (Solvent A) and MeOH (Solvent B)
  10. custom1 min
  11. custom15 min
  12. additionThe fractions containing product
  13. concentrationconcentrated to dryness under vacuum

Sources & evidence

ORD record
ord-f94272e548a34f04bdff90e3e2f64abd
Source dataset
uspto-grants-2015_08
Patent number
US09115088B2

Reaction notes

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