Iodine → 4-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-(tert-butyldimethylsilyloxy)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

HRID 470752Notes

Reaction equation

HRID 470752 reaction equation
[Si:1]([O:8][C:9]1[CH:42]=[CH:41][C:12]([C:13]([NH:15][NH:16][C:17](=O)[C@H:18]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]#[N:37])=[C:32]([Cl:38])[C:31]=2[CH3:39])[C@H:19]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH3:20])=[O:14])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.II.[Si](O[C@@H](C)[C@@H](NC1C=CC(C#N)=C(Cl)C=1C)C1OC(C2C=CC=C(O[Si](C(C)(C)C)(C)C)C=2)=NN=1)(C(C)(C)C)(C)C>>[Si:22]([O:21][C@H:19]([CH3:20])[C@@H:18]([NH:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]#[N:37])=[C:32]([Cl:38])[C:31]=1[CH3:39])[C:17]1[O:14][C:13]([C:12]2[CH:41]=[CH:42][C:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2])=[CH:10][CH:11]=2)=[N:15][N:16]=1)([C:25]([CH3:26])([CH3:27])[CH3:28])([CH3:23])[CH3:24]

Participants

5

Reactant 4

HCID 807IodineHCID 11776TriphenylphosphineHCID 67005760HCID 67005760, compoundHCID 67006501HCID 67006501, compound2×

Product 1

HCID 670065564-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-(tert-butyldimethylsilyloxy)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

Procedure

4-(tert-butyldimethylsilyloxy)-N′-((2R,3R)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)benzohydrazide (intermediate 10b) (202 mg, 0.3 mmol) was cyclized with PS-PPh3 (3.0 mmol/g, 209 mg, 0.63 mmol), I2 (152 mg, 0.6 mmol), and TEA (0.33 mL, 2.4 mmol) as described for the preparation of intermediate 7c. After column chromatography (20% EtOAc/hexanes) the title compound was isolated as a white solid (147 mg, 75%). 1H NMR (500 MHz, CDCl3, δ in ppm) 7.86 (AA′XX′, J=8.7 Hz, 2H), 7.34 (d, J=8.6 Hz, 1H), 6.91 (AA′XX′, J=8.7 Hz, 2H), 6.62 (d, J 8.7 Hz, 1H), 5.11 (d, J=8.8 Hz, 1H), 4.81 (dd, J=3.9, 8.8 Hz, 1H), 4.43 (m, 1H), 2.32 (s, 3H), 1.28 (d, J=6.3 Hz, 3H), 0.98 (s, 9H), 0.93 (s, 9H), 0.22 (s, 6H), 0.13 (s, 3H), 0.10 (s, 3H).

Sources & evidence

ORD record
ord-3b9ed48356a24b6fa90ea48bc6f1c0e2
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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