Dichloromethane → HCID 16755043, compound

HRID 1992423Notes

Reaction equation

HRID 1992423 reaction equation
I[C:2]1[N:3]=[C:4]([S:12][CH3:13])[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.C([N:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[C:22]1B(O)O)(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O.C(OCC)(=O)C.CO.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]>[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[C:22]1[C:2]1[N:3]=[C:4]([S:12][CH3:13])[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)HCID 16755135HCID 16755135, compound

Product 1

HCID 16755043HCID 16755043, compound

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 1-iodo-3-methylsulfanyl-imidazo[1,5-a]pyrazin-8-ylamine (612 mg, 0.00200 mol) in 1,4-dioxane (20 mL) and water (5 mL) were added 1-Boc-indole-2-boronic acid (570 mg, 0.0022 mol), potassium carbonate (830 mg, 0.0060 mol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (80 mg, 0.0001 mol). The flask was evacuated and refilled with nitrogen (3×). The mixture was heated at 100° C. overnight. LC-MS showed the reaction to be incomplete. Another 80 mg of PdCl2(dppf) was added and the mixture was heated at 100° C. overnight. LC-MS showed the reaction was complete. The mixture was diluted with ethyl acetate (100 mL) and methanol (5 mL); the insoluble solid was filtered off through a pad of celite. The filtrate was washed with brine (20 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hex:EtOAc=30:70→EtOAc:MeOH=98:2) to give the title compound as a yellow solid. LC-MS (ES, Pos.): 296 [MH+]; 1H-NMR (DMSO-d6): δ 2.64 (s, 3H), 6.58 (br s, 2H), 6.70 (d, J=1.5 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 7.13 (m, 1H), 7.18 (d, J=4.8 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.53 (d, J=4.8 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 11.60 (s, 1H).

Workup

  1. customThe flask was evacuated
  2. additionrefilled with nitrogen (3×)
  3. customthe reaction
  4. temperaturethe mixture was heated at 100° C. overnight
  5. filtrationthe insoluble solid was filtered off through a pad of celite
  6. washThe filtrate was washed with brine (20 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe crude material was purified by silica gel chromatography (Hex:EtOAc=30:70→EtOAc:MeOH=98:2)

Sources & evidence

ORD record
ord-735fa4026c284628803ca215b4650c1c
Source dataset
uspto-grants-2010_01
Patent number
US07648987B2

Reaction notes

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