Sodium Carbonate → HCID 67959840, compound

HRID 1529258Notes

Reaction equation

HRID 1529258 reaction equation
Cl.Cl.Br[C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[C:7]2[C:13]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]2)[CH:16]=[N:15][CH:14]=1.[CH:26]1([NH:29][C:30]([C:32]2[CH:33]=[CH:34][C:35]([F:41])=[C:36](B(O)O)[CH:37]=2)=[O:31])[CH2:28][CH2:27]1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[NH2:25][CH:22]1[CH2:23][CH2:24][N:19]([C:17]2[N:18]=[C:13]([C:7]3[C:6]4[C:10](=[CH:11][CH:12]=[C:4]([C:34]5[CH:33]=[C:32]([CH:37]=[CH:36][C:35]=5[F:41])[C:30]([NH:29][CH:26]5[CH2:27][CH2:28]5)=[O:31])[CH:5]=4)[NH:9][N:8]=3)[CH:14]=[N:15][CH:16]=2)[CH2:20][CH2:21]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 46738921[5-(Cyclopropylcarbamoyl)-2-fluorophenyl]boronic acidHCID 67959848HCID 67959848, compound

Product 1

HCID 67959840HCID 67959840, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a 5 mL conical microwave vial was added Pd(dppf)Cl2 (15.53 mg, 0.02 mmol), 1-(6-(5-bromo-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-amine dihydrochloride salt (Example 1) (71 mg, 0.19 mmol), and 5-(cyclopropylcarbamoyl)-2-fluorophenylboronic acid (46.7 mg, 0.21 mmol), capped, degassed and backfilled with argon (3×). Dioxane (1.9 mL) and 2N Na2CO3 aqueous solution (0.2 mL, 0.48 mmol) were added. The reaction mixture was stirred at 80° C. for 16 h. After cooling to RT, the reaction mixtures were filtered before concentrating under reduced pressure. The crude reaction mixture was purified by preparative HPLC using water with 0.1% NH4OH and ACN with 0.1% NH4OH (Column: Phenomenex Gemini-NX C18 110 A 5 μm, 21×100 mm) to afford the title compound. MS (ESI, pos. ion) m/z: 472 (M+1).

Workup

  1. customcapped
  2. customdegassed
  3. temperatureAfter cooling to RT
  4. customthe reaction mixtures
  5. filtrationwere filtered
  6. concentrationbefore concentrating under reduced pressure
  7. customThe crude reaction mixture
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-93d1ea00b5174afd80650fa2d1351087
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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