Triethylamine → 4-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

HRID 1254752Notes

Reaction equation

HRID 1254752 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(CC)CC.[Si:27]([O:34][C@@H:35]([CH3:61])[C@@H:36]([NH:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]#[N:58])=[C:53]([Cl:59])[C:52]=1[CH3:60])[C:37]([NH:39][NH:40][C:41](=[O:49])[C:42]1[CH:47]=[CH:46][C:45]([I:48])=[CH:44][CH:43]=1)=O)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>C(Cl)Cl>[Si:27]([O:34][C@@H:35]([CH3:61])[C@@H:36]([NH:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]#[N:58])=[C:53]([Cl:59])[C:52]=1[CH3:60])[C:37]1[O:49][C:41]([C:42]2[CH:43]=[CH:44][C:45]([I:48])=[CH:46][CH:47]=2)=[N:40][N:39]=1)([C:30]([CH3:32])([CH3:33])[CH3:31])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67005875N'-((2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-iodobenzohydrazide

Product 1

HCID 670064554-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrileYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of triphenylphosphine (7.2 g, 27.5 mmol) in DCM (300 mL) was added 12 (7.0 g, 27.5 mmol) at 0° C. After 12 was dissolved completely, Et3N (7.7 mL, 55.2 mmol) was added, followed by a solution of N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-iodobenzohydrazide (8.6 g, 13.7 mmol) in DCM (100 mL). The reaction mixture was allowed to warm to room temperature and stirred for an additional 60 min. The reaction was quenched with saturated sodium thiosulfate (50 mL) and diluted with DCM (500 mL). The organic layer was separated and washed with water, brine, dried over Na2SO4 and filtered. After the solvent was removed, the residue was purified by flash chromatography to provide the title compound (7.3 g, 88%). 1H NMR (400 MHz, CDCl3, δ in ppm) 8.06 (d, J=8.6 Hz, 2H), 7.88 (d, J=8.6 Hz, 2H), 7.55 (d, J=8.4 Hz, 1H), 6.66 (d, J=8.4 Hz, 1H), 5.56 (d, J=8.8 Hz, 1H), 5.00 (dd, J=2.0, 8.8 Hz, 1H), 4.74 (m, 1H), 2.59 (s, 3H), 1.62 (d, J=6.3 Hz, 3H), 1.07 (s, 9H), 0.28 (s, 3H), 0.00 (s, 3H).

Workup

  1. dissolutionAfter 12 was dissolved completely
  2. customThe reaction was quenched with saturated sodium thiosulfate (50 mL)
  3. additiondiluted with DCM (500 mL)
  4. customThe organic layer was separated
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customAfter the solvent was removed
  9. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-ea013b2b8e0f4603bff1acefbf411f5a
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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