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Methanol → HCID 178493783, compound

HRID 525277
Notes
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Reaction equation

HRID 525277 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@@H:12]([O:15][C:16]3[CH:25]=[C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[CH:23]=[C:22]4[C:17]=3[N:18]=[CH:19][CH:20]=[N:21]4)[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[C:32](=O)([O-])[O-:33].[Cs+].[Cs+].CO>C1(C)C=CC=CC=1.[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].CC1C=CC(OC)=C(P(C(C)(C)C)C(C)(C)C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C>[CH3:32][O:33][C:2]1[CH:3]=[N:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@@H:12]([O:15][C:16]3[CH:25]=[C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[CH:23]=[C:22]4[C:17]=3[N:18]=[CH:19][CH:20]=[N:21]4)[CH2:11][CH2:10]2)=[N:6][CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 887MethanolHCID 10796Cesium carbonateHCID 178419459HCID 178419459, compound

Product 1

HCID 178493783HCID 178493783, compoundYield 63.6%

Reagents, catalysts & solvents 3

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-Catalyst
HCID 56641709
(2',4'-Diisopropyl-3-methoxy-6-methyl-6'-propyl-2-biphenylyl)[bis(2-methyl-2-propanyl)]phosphine
Catalyst
HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

As shown in step 6-ix of Scheme 6, to a mixture 5-bromo-N-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine (75 mg, 0.155 mmol), cesium carbonate (101 mg, 0.309 mmol), allylpalladium(II) chloride dimer (0.28 mg, 0.0015 mmol), RockPhos (2.17 mg, 0.0046 mmol) and MeOH (9.9 mg, 12.5 μL, 0.31 mmol) in toluene (2 mL) was flushed with nitrogen gas and heated to 100° C. for 18 hours. The reaction mixture was iluted with EtOAc, filtered though a layer of diatomaceous earth, and concentrated under reduced pressure. Purification by medium pressure silica gel chromatography (0-8% MeOH/DCM gradient) yielded 5-methoxy-N-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine (compound 134, 43 mg): 1H-NMR (300 MHz, CDCl3) δ 8.70 (d, J=1.9 Hz, 1H), 8.63 (d, J=1.9 Hz, 1H), 8.07 (s, 2H), 6.96 (d, J=2.5 Hz, 1H), 6.92 (d, J=2.5 Hz, 1H), 5.01 (d, J=8.1 Hz, 1H), 4.80 (q, J=5.6, 4.2 Hz, 1H), 4.03-3.87 (m, 5H), 3.80 (s, 3H), 3.42-3.27 (m, 4H), 2.29-2.10 (m, 2H), 1.99-1.82 (m, 6H).

Workup

  1. customwas flushed with nitrogen gas
  2. filtrationfiltered though a layer of diatomaceous earth
  3. concentrationconcentrated under reduced pressure
  4. customPurification by medium pressure silica gel chromatography (0-8% MeOH/DCM gradient)

Sources & evidence

ORD record
ord-d6003b3d339d450aa097cff3708b1d00
Source dataset
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09340557B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes