Piperidine → HCID 86693524, compound

HRID 575461Notes

Reaction equation

HRID 575461 reaction equation
[F:1][C:2]1([F:20])[CH2:8][O:7][C:6]2[CH:9]=[CH:10][C:11](I)=[CH:12][C:5]=2[N:4]2[N:14]=[C:15]([C:17]([NH2:19])=[O:18])[CH:16]=[C:3]12.N1CCCCC1.[CH3:27][C:28]1[O:32][N:31]=[C:30]([C@:33]([OH:37])([C:35]#[CH:36])[CH3:34])[CH:29]=1>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>[F:1][C:2]1([F:20])[CH2:8][O:7][C:6]2[CH:9]=[CH:10][C:11]([C:36]#[C:35][C@@:33]([OH:37])([C:30]3[CH:29]=[C:28]([CH3:27])[O:32][N:31]=3)[CH3:34])=[CH:12][C:5]=2[N:4]2[N:14]=[C:15]([C:17]([NH2:19])=[O:18])[CH:16]=[C:3]12

Participants

6

Reactant 3

HCID 8082PiperidineHCID 58221468(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-olHCID 86693525HCID 86693525, compound

Product 1

HCID 86693524HCID 86693524, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
60 °C

Procedure

To a pressure tube was added 4,4-difluoro-9-iodo-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-2-carboxamide (65 mg, 0.17 mmol) followed by piperidine (1.5 ml), tetrakis(triphenylphosphine)palladium (0) (19.2 mg, 0.02 mmol), copper(I) iodide (3.2 mg, 0.02 mmol) and (2R)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (38 mg, 0.25 mmol). The reaction vessel was sealed and heated at 60° C. for 40 minutes. The reaction mixture was cooled and concentrated in vacuo. and then co-evaporated with dichloromethane (2×10 ml). The crude material was purified by FCC (silica, 1-8% methanol in dichloromethane) to provide 34 mg (49%) of the title compound as a pale brown solid. 1H-NMR (500 MHz, DMSO-d6): 1.81 (3H, s), 2.41 (3H, d, J=0.7 Hz), 4.85 (2H, t, J=11.7 Hz), 6.36 (1H, d, J=0.8 Hz), 6.56 (1H, s), 7.33 (1H, d, J=8.4 Hz), 7.35 (1H, s), 7.43 (1H, dd, J=8.4, 2.0 Hz), 7.60 (1H, s), 8.16 (1H, s), 8.37 (1H, d, J=2.0 Hz); M+23=437.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by FCC (silica, 1-8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-417d410936c64f9690c0205af6b76d69
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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