Sodium Carbonate → HCID 67284974, compound

HRID 2409575Notes

Reaction equation

HRID 2409575 reaction equation
I[C:2]1[N:9]2[C:5]([S:6][C:7]([C:10]3[CH:11]=[C:12]4[C:18]5([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]5)[C:17](=[O:31])[NH:16][C:13]4=[CH:14][CH:15]=3)=[N:8]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[C:42]([C:47]([F:50])([F:49])[F:48])[C:43]([NH2:46])=[N:44][CH:45]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(Cl)Cl.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]>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][C:18]2([C:12]3[C:13](=[CH:14][CH:15]=[C:10]([C:7]4[S:6][C:5]5=[N:4][CH:3]=[C:2]([C:40]6[CH:41]=[C:42]([C:47]([F:50])([F:49])[F:48])[C:43]([NH2:46])=[N:44][CH:45]=6)[N:9]5[N:8]=4)[CH:11]=3)[NH:16][C:17]2=[O:31])[CH2:19][CH2:20]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 66717017HCID 66717017, compound

Product 1

HCID 67284974HCID 67284974, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-Iodo-2-(1′-(tert-butoxycarbonyl)-2-oxo-1,2-dihydrospiro[indole-3,4′-piperidine]-5-yl)-imidazo[2,1-b][1,3,4]thiadiazole (46 mg, 0.082 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (31 mg, 0.106 mmol), PdCl2(dppf) (13 mg, 0.016 mmol) and sat Na2CO3 (0.41 mL) in DME (0.82 mL) was heated under microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with DCM and washed with H2O. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography (Isolute/Flash, Sill, 0% to 5% MeOH in DCM) to give the desired product (19.5 mg, 41%) as a yellow solid. HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=5.77 min, [M+H]+ m/z 586.2; 1H NMR (300 MHz, DMSO) δ 10.90 (s, 1H), 8.87 (d, J=1.8 Hz, 1H), 8.43 (d, J=2.0 Hz, 1H), 8.01 (d, J=1.6 Hz, 1H), 7.83 (dd, J=8.1, 1.7 Hz, 1H), 7.77 (s, 1H), 7.07 (d, J=8.2 Hz, 1H), 6.72 (s, 2H), 3.71 (s, 4H), 1.77 (m, 4H), 1.46 (s, 9H).

Workup

  1. washwashed with H2O
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (Isolute/Flash, Sill, 0% to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-23a6c258f5d54ef6aab53039b3168858
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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