(R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol → (2R)-4-[1-(2-aminopyrimidin-4-yl)-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

HRID 1398683Notes

Reaction equation

HRID 1398683 reaction equation
[F:1][CH2:2][CH2:3][O:4][C:5]1[N:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=2)[C:8]2[CH:17]=[C:18](I)[CH:19]=[CH:20][C:7]=2[N:6]=1.[CH3:22][C:23]1[O:27][N:26]=[C:25]([C@:28]([OH:32])([C:30]#[CH:31])[CH3:29])[N:24]=1>C(N(CC)CC)C.CS(C)=O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:16][C:12]1[N:11]=[C:10]([N:9]2[C:8]3[CH:17]=[C:18]([C:31]#[C:30][C@:28]([C:25]4[N:24]=[C:23]([CH3:22])[O:27][N:26]=4)([OH:32])[CH3:29])[CH:19]=[CH:20][C:7]=3[N:6]=[C:5]2[O:4][CH2:3][CH2:2][F:1])[CH:15]=[CH:14][N:13]=1

Participants

7

Reactant 2

HCID 86669593(R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-olHCID 866696094-[2-(2-fluoroethoxy)-6-iodo-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine

Product 1

HCID 86669610(2R)-4-[1-(2-aminopyrimidin-4-yl)-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-olYield 7.2%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-[2-(2-fluoroethoxy)-6-iodo-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (130 mg, 0.33 mmol), (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (148 mg, 0.97 mmol), bis(triphenylphosphine)palladium(II) dichloride (34 mg, 0.05 mmol) in triethylamine (1 mL) and dimethylsulfoxide (1 mL) was irradiated with microwave radiation under nitrogen in a 8-mL vial at 90° C. for 30 min. The resulting solution was cooled to room temperature and diluted with 30 mL of ethyl acetate. The solid material was removed by filtration. The residue was concentrated under vacuum then purified on a silica gel column (ethyl acetate/petroleum ether, 2:1) to give 10 mg (7%) of (2R)-4-[1-(2-aminopyrimidin-4-yl)-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol as a light brown solid. 1H NMR (400 MHz, MeOD) delta 8.47 (s, 1H), 8.35 (d, J=5.6 Hz, 1H), 7.44 (d, J=8.4 Hz, 1H), 7.39-7.36 (m, 1H), 7.15 (d, J=5.6 Hz, 1H), 4.95-4.90 (m, 2H), 4.85-4.81 (m, 2H), 2.63 (s, 3H), 1.96 (s, 3H); LC-MS: m/z=+424 (M+H)+.

Workup

  1. customThe solid material was removed by filtration
  2. concentrationThe residue was concentrated under vacuum
  3. customthen purified on a silica gel column (ethyl acetate/petroleum ether, 2:1)

Sources & evidence

ORD record
ord-874aed2339e34336b71e3d57ba17e03a
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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