HCID 86675871, compound → HCID 71225351, compound

HRID 1895801Notes

Reaction equation

HRID 1895801 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) δ 0.16 (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-94f22e25d249428abb03c8a639f79207
Source dataset
uspto-grants-2013_08
Patent number
US08513184B2

Reaction notes

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