4-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine → N-isopropyl-5-(3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

HRID 634324Notes

Reaction equation

HRID 634324 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:15][C:14]([NH:16][CH:17]([CH3:19])[CH3:18])=[N:13][N:12]=3)[CH:9]=2)[N:4]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:3]=1.[CH3:30][O:31][C:32]1[CH:53]=[CH:52][C:35]([CH2:36][O:37][C:38]2[CH:43]=[C:42]([Sn](C)(C)C)[N:41]=[C:40]([S:48]([CH3:51])(=[O:50])=[O:49])[N:39]=2)=[CH:34][CH:33]=1>CN(C=O)C.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.[Cu]I>[CH:17]([NH:16][C:14]1[O:15][C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([S:20]([C:23]2[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=2)(=[O:22])=[O:21])[CH:3]=[C:2]3[C:42]2[CH:43]=[C:38]([O:37][CH2:36][C:35]3[CH:34]=[CH:33][C:32]([O:31][CH3:30])=[CH:53][CH:52]=3)[N:39]=[C:40]([S:48]([CH3:51])(=[O:50])=[O:49])[N:41]=2)=[N:12][N:13]=1)([CH3:18])[CH3:19]

Participants

6

Reactant 2

HCID 679579354-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidineHCID 683289275-(3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Product 1

HCID 68328463N-isopropyl-5-(3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 62.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (800 mg, 1.532 mmol) and 4-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine (875 mg, 1.914 mmol) in DMF (5 mL) followed by Pd(PPh3)4 (88 mg, 0.077 mmol) and CuI (72.9 mg, 0.383 mmol). The reaction mixture was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 1 h. The mixture was filtered through a plug of celite and washed with DCM. The filtrate was washed with water (25 mL×3) and the organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 10-20% EtOAc in DCM with 1% MeOH) to give N-isopropyl-5-(3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (660 mg, 0.958 mmol, 62.6% yield) as a brown solid. MS (ESI, pos. ion) m/z: 688.8 (M+1).

Workup

  1. customA glass microwave reaction vessel
  2. filtrationThe mixture was filtered through a plug of celite
  3. washwashed with DCM
  4. washThe filtrate was washed with water (25 mL×3)
  5. customthe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography (eluting with 10-20% EtOAc in DCM with 1% MeOH)

Sources & evidence

ORD record
ord-605585437d474aaaa1a13432268f2278
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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