Water → HCID 16753770, compound

HRID 1992440Notes

Reaction equation

HRID 1992440 reaction equation
Br[C:2]1[N:3]=[C:4]([S:12][C:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.[F:17][C:18]1[C:19](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:21]=[C:22]2[C:27]=1[N:26]=[C:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH:24]=[CH:23]2.[F-].[K+].COCCOC.O.CN(C=O)C>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>[C:13]([S:12][C:4]1[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]2=[C:2]([C:19]2[C:18]([F:17])=[C:27]3[C:22]([CH:23]=[CH:24][C:25]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[N:26]3)=[CH:21][CH:20]=2)[N:3]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 6

HCID 962WaterHCID 6228DimethylformamideHCID 80711,2-DimethoxyethaneHCID 522689Potassium FluorideHCID 16753771HCID 16753771, compoundHCID 536290468-Fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline

Product 1

HCID 16753770HCID 16753770, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

Into a 10 mL microwave vessel was added 1-bromo-3-tert-butylsulfanyl-imidazo[1,5-a]pyrazin-8-ylamine (23 mg, 0.000076 mol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (0.032 g, 0.000092 mol), potassium fluoride (0.0089 g, 0.00015 mol), DME (2 mL, 0.02 mol), H2O (0.3 mL, 0.02 mol), DMF (0.34 mL, 0.0044 mol) and the reaction mixture was degassed 3×. Pd(PPh3)4 (0.02 g, 0.00002 mol) was then added to the reaction mixture and the vessel was sealed. The reaction mixture was microwaved on 300 watts, 100° C. for 30 min. Reaction mixture was concentrated in vacuo. Purification by Gilson HPLC eluting with 10→75% acetonitrile: H2O afforded the compound with pinacole impurity. The compound was then passed through a 2 g silica gel cartridge eluting with 6% EtOAc in hexanes followed by 4% MeOH in DCM to afford the pure compound as a yellow solid. 1H NMR (400 MHz, CD3OD-d4): δ=1.43 (s, 9H), 7.22 (d, J=5.05 Hz, 1H), 7.50-7.59 (m, 3H), 7.68-7.74 (m, 1H), 7.90-7.96 (m, 2H), 8.20 (d, J=8.59 Hz, 1H), 8.26 (d, J=7.83 Hz, 2H), 8.51 (dd, J=8.84, 1.26 Hz, 1H). MS(ES+):m/z 444.17 (100)[MH+]. HPLC: tR=3.24 min (Open Lynx polar—5 min).

Workup

  1. customthe reaction mixture was degassed 3×
  2. customthe vessel was sealed
  3. customThe reaction mixture was microwaved on 300 watts, 100° C. for 30 min
  4. customReaction mixture
  5. concentrationwas concentrated in vacuo
  6. customPurification by Gilson HPLC
  7. washeluting with 10→75% acetonitrile
  8. customH2O afforded the compound with pinacole impurity
  9. washeluting with 6% EtOAc in hexanes

Sources & evidence

ORD record
ord-bd76c81a6dcb422cbce4085adcfe5a8d
Source dataset
uspto-grants-2010_01
Patent number
US07648987B2

Reaction notes

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