Sodium Carbonate → HCID 178419829, compound

HRID 2200778Notes

Reaction equation

HRID 2200778 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([O:12][C@@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20]3[N:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[CH2:15][CH2:14]2)[CH:3]=1.[O:26]1[CH2:31][CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH2:28][CH2:27]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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]>[O:26]1[CH2:27][CH:28]=[C:29]([C:2]2[CH:11]=[C:10]3[C:5]([N:6]=[CH:7][CH:8]=[N:9]3)=[C:4]([O:12][C@@H:13]3[CH2:18][CH2:17][C@H:16]([NH:19][C:20]4[N:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[CH2:15][CH2:14]3)[CH:3]=2)[CH2:30][CH2:31]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol ester2×HCID 178419414HCID 178419414, compound2×

Product 1

HCID 178419829HCID 178419829, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

As shown in step 8-ii of Scheme 8, a mixture of N-((cis)-4-((7-bromoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine (compound 1025, 52 mg, 0.1299 mmol), Pd(dppf)Cl2 (10.61 mg, 0.01299 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (compound 1026, 27.3 mg, 0.13 mmol), Na2CO3 (195 μL of 2M (aq) solution, 0.39 mmol) in DMF (1 mL) was flushed with nitrogen gas for 10 minutes. The mixture was subjected to microwave radiation for 20 min at 150° C. After cooling, the mixture was diluted with EtOAc, washed with H2O, dried over Na2SO4, concentrated under reduced pressure and purified by medium pressure silica gel chromatography (0-5% MeOH/DCM) to provide N-[(cis)-4-[7-(3,6-dihydro-2H-pyran-4-yl)quinoxalin-5-yl]oxycyclohexyl]pyrimidin-2-amine (compound 36) as an off-white solid: 1H-NMR (300 MHz, CDCl3) δ 8.94-8.76 (m, 2H), 8.29 (d, J=4.8 Hz, 2H), 7.67 (d, J=1.7 Hz, 1H), 6.53 (t, J=4.8 Hz, 1H), 6.37 (tt, J=3.1, 1.5 Hz, 1H), 5.30 (d, J=7.9 Hz, 1H), 4.87 (dt, J=7.5, 3.6 Hz, 1H), 4.43 (q, J=2.8 Hz, 2H), 4.02 (t, J=5.5 Hz, 3H), 2.68 (dqd, J=6.0, 3.4, 3.0, 1.8 Hz, 2H), 2.35-2.11 (m, 2H), 2.07-1.84 (m, 6H); ESMS (M+H+)=404.2.

Workup

  1. customwas flushed with nitrogen gas for 10 minutes
  2. customfor 20 min
  3. customat 150° C
  4. temperatureAfter cooling
  5. additionthe mixture was diluted with EtOAc
  6. washwashed with H2O
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. custompurified by medium pressure silica gel chromatography (0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-5ddb9e2f9fc34baa859d1af5fdde4e4a
Source dataset
uspto-grants-2016_06
Patent number
US09359380B2

Reaction notes

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