HCID 67960517, compound → HCID 71225675, compound

HRID 1895792Notes

Reaction equation

HRID 1895792 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][O:10][C:11]([C@@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:55])[C@@H:20]([NH:36][C:37](=[O:54])[C@@H:38]([NH:42][C:43](=[O:53])[C@H:44]([CH3:52])[C@H:45]([O:50][CH3:51])[CH2:46][CH2:47]C=C)[CH:39]([CH3:41])[CH3:40])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH:23]=3)[NH:14]2)=[O:12])[CH:4]=1)=[CH2:2]>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:32]([Si:29]([CH3:30])([CH3:31])[O:28][C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[CH2:21][C@H:20]1[C:19](=[O:55])[N:15]2[NH:14][C@@H:13]([CH2:18][CH2:17][CH2:16]2)[C:11](=[O:12])[O:10][CH2:9][C:5]2=[CH:4][C:3](=[CH:8][CH:7]=[N:6]2)[CH:1]=[CH:2][CH2:47][CH2:46][C@@H:45]([O:50][CH3:51])[C@@H:44]([CH3:52])[C:43](=[O:53])[NH:42][C@@H:38]([CH:39]([CH3:41])[CH3:40])[C:37](=[O:54])[NH:36]1)([CH3:35])([CH3:33])[CH3:34]

Participants

4

Reactant 1

HCID 67960517HCID 67960517, compound

Product 1

HCID 71225675HCID 71225675, compoundYield 61%

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

Conditions

Temperature
80 °C

Procedure

Hoveyda-Grubbs 2nd generation catalyst (22 mg, 0.035 mmol) was added to a stirred solution of (S)-1-{(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[(S)-2-((2R,3R)-3-methoxy-2-methyl-hept-6-enoylamino)-3-methyl-butyrylamino]-prop ionyl}-hexahydro-pyridazine-3-carboxylic acid 4-vinyl-pyridin-2-ylmethyl ester (276 mg, 0.35 mmol) in 1,2-dichloroethane (130 mL) and the reaction mixture was heated at 80° C. under nitrogen for 3 hours. The reaction mixture was cooled to room temperature, silica gel was added and the solvent was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:1 to neat ethyl acetate to afford (E)-(1S,14R,15R,18S,21S)-21-[3-(tert-butyl-dimethyl-silanyloxy)-benzyl]-18-isopropyl-14-methoxy-15-methyl-3-oxa-6,17,20,23,27-pentaaza-tricyclo[21.3.1.1*5,9*]octacosa-5(28),6,8,10-tetraene-2,16,19,22-tetraone (160 mg, 61%) as a white solid. LCMS (m/z) 750 [M+H], Tr=5.58 min.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionsilica gel was added
  3. customthe solvent was evaporated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6e693d1664b9483eb565a74cb88774e3
Source dataset
uspto-grants-2013_08
Patent number
US08513184B2

Reaction notes

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