Nitrogen → 5-(3-(6-(isopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-3-amine

HRID 634271Notes

Reaction equation

HRID 634271 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:15][N:14]=[C:13]([NH2:16])[N:12]=3)[CH:9]=2)[NH:4][CH:3]=1.[CH:17]([NH:20][C:21]1[CH:26]=[N:25][CH:24]=[C:23]([Sn](CCCC)(CCCC)CCCC)[N:22]=1)([CH3:19])[CH3:18].N#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:17]([NH:20][C:21]1[N:22]=[C:23]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[O:15][N:14]=[C:13]([NH2:16])[N:12]=4)[CH:9]=3)[NH:4][CH:3]=2)[CH:24]=[N:25][CH:26]=1)([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 947Nitrogen2×HCID 68328197N-isopropyl-6-(tributylstannyl)pyrazin-2-amineHCID 68328272HCID 68328272, compound

Product 1

HCID 683289115-(3-(6-(isopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-3-amineYield 10%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of 5-(3-iodo-1H-indol-5-yl)-1,2,4-oxadiazol-3-amine (0.15 g, 0.460 mmol) and isopropyl-(6-tributylstannanyl-pyrazin-2-yl)-amine (0.235 g, 0.549 mmol) was bubbled N2 gas for 15 min. To the mixture was added Cut (0.070 g, 0.366 mmol) and Pd(PPh3)4 (0.053 g, 0.043 mmol) and N2 gas was bubbled for another 15 min. The reaction was heated at 90° C. for 1 h. The mixture was cooled to RT, quenched with H2O (100 mL) and extracted with EtOAc (2×100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified with preparative HPLC (eluent: 10-60% AcCN in H2O with 0.01% TFA) to give 5-(3-(6-(isopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-3-amine (0.015 g, 10%) as a pale yellow solid. MS (ESI, pos. ion) m/z: 336.2 (M+1); 1H-NMR (400 MHz, CD3OD): δ 9.34 (s, 1H), 8.09 (s, 1H), 8.04 (d, J=0.8 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H), 4.39 (m, 1H), 1.38 (dd, J=6.8, 1.2 Hz, 6H).

Workup

  1. customwas bubbled for another 15 min
  2. temperatureThe mixture was cooled to RT
  3. customquenched with H2O (100 mL)
  4. extractionextracted with EtOAc (2×100 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified with preparative HPLC (eluent: 10-60% AcCN in H2O with 0.01% TFA)

Sources & evidence

ORD record
ord-80a66754b2504e1fabde8c4430001998
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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