HCID 86675871, compound → HCID 71225351, compound

HRID 1427790Notes

Reaction equation

HRID 1427790 reaction equation
C([C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12]([C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([C:20](=[O:55])[C@@H:21]([NH:37][C:38](=[O:54])[C@@H:39]([NH:43][C:44](=[O:53])[CH2:45][C@H:46]([O:51][CH3:52])[CH2:47][CH2:48][CH:49]=[CH2:50])[CH:40]([CH3:42])[CH3:41])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH:24]=3)[NH:15]2)=[O:13])[CH3:10])[CH:6]=[CH:7][CH:8]=1)=C>CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.ClCCCl>[C:33]([Si:30]([CH3:31])([CH3:32])[O:29][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[CH2:22][C@@H:21]1[NH:37][C:38](=[O:54])[C@H:39]([CH:40]([CH3:42])[CH3:41])[NH:43][C:44](=[O:53])[CH2:45][C@H:46]([O:51][CH3:52])[CH2:47][CH2:48][CH:49]=[CH:50][C:7]2=[CH:6][C:5](=[CH:4][CH:3]=[CH:8]2)[C@@H:9]([CH3:10])[O:11][C:12](=[O:13])[C@H:14]2[NH:15][N:16]([CH2:17][CH2:18][CH2:19]2)[C:20]1=[O:55])([CH3:35])([CH3:36])[CH3:34]

Participants

4

Reactant 1

HCID 86675871HCID 86675871, compound

Product 1

HCID 71225351HCID 71225351, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 111,2-DichloroethaneSolvent

Procedure

A stirred solution of (S)-1-{(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[(S)-2-((R)-3-methoxy-hept-6-enoylamino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (R)-1-(3-vinyl-phenyl)-ethyl ester (123 mg, 0.158 mmol) and Hoveyda-Grubbs 2nd generation catalyst (10 mg, 0.0158 mmol) in 1,2-dichloroethane (60 mL) was heated at 80° C. for 1.5 hours. The reaction mixture was cooled before adding silica gel. The mixture was evaporated then purified by silica gel chromatography using ethyl acetate to give the title compound (54 mg, 46%) as a pale brown solid. 1H NMR (300 MHz, CDCl3) δ0.16 (s, 6H), 0.80-1.00 (m, 17H), 1.34-1.94 (m, 12H), 2.00-2.20 (m, 5H), 2.34-2.53 (m, 3H), 2.63-3.03 (m, 3H), 3.38 (s, 3H), 3.52-3.70 (m, 2H), 4.27-4.38 (m, 2H), 4.92-5.10 (m, 2H), 5.29 (d, J=10.9 Hz, 1H), 5.64-5.98 (m, 2H), 6.52-6.99 (m, 4H), 7.22-7.42 (m, 2H). LCMS (m/z) 749.3 [M+H] Tr=5.91 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. additionbefore adding silica gel
  3. customThe mixture was evaporated
  4. customthen purified by silica gel chromatography

Sources & evidence

ORD record
ord-06fe0ac2c5184bc69d5193990b2b878e
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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