(S)-ethyl 2-(2-((2-allylbenzamido)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate → ethyl (2S)-2-(tert-butoxy)-2-[(20E)-4,24-dimethyl-12-oxo-23-oxa-1,5,7,8,11-pentaazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16,20-octaen-3-yl]acetate

HRID 921094Notes

Reaction equation

HRID 921094 reaction equation
[CH2:1]([C:4]1[CH:45]=[CH:44][CH:43]=[CH:42][C:5]=1[C:6]([NH:8][CH2:9][C:10]1[CH:41]=[C:13]2[N:14]=[C:15]([CH3:40])[C:16]([C@H:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:17]([N:18]3[CH2:23][CH2:22][C:21]([O:25][CH2:26][CH:27]=C)([CH3:24])[CH2:20][CH2:19]3)[N:12]2[N:11]=1)=[O:7])[CH:2]=C>ClCCCl.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>[C:36]([O:35][C@@H:29]([C:16]1[C:15]([CH3:40])=[N:14][C:13]2=[CH:41][C:10]3=[N:11][N:12]2[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:24])([O:25][CH2:26][CH:27]=[CH:2][CH2:1][C:4]2[CH:45]=[CH:44][CH:43]=[CH:42][C:5]=2[C:6](=[O:7])[NH:8][CH2:9]3)[CH2:20][CH2:19]1)[C:30]([O:32][CH2:33][CH3:34])=[O:31])([CH3:38])([CH3:39])[CH3:37]

Participants

4

Reactant 1

HCID 118318759(S)-ethyl 2-(2-((2-allylbenzamido)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 131734903ethyl (2S)-2-(tert-butoxy)-2-[(20E)-4,24-dimethyl-12-oxo-23-oxa-1,5,7,8,11-pentaazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16,20-octaen-3-yl]acetate

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

To a stirred solution of (S)-ethyl 2-(2-((2-allylbenzamido)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.058 g, 0.094 mmol) in 1,2-dichloroethane (20 mL) at 70° C. was added Hoveyda-Grubbs catalyst 2nd generation (2.94 mg, 4.69 μmol) and refluxed for 2 h. Then, cooled, concentrated and the resulting residue was purified by flash chromatography using 1:1 and 1:3 Hex/EtOAc to afford ethyl (2S)-2-(tert-butoxy)-2-[(20E)-4,24-dimethyl-12-oxo-23-oxa-1,5,7,8,11-pentaazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16,20-octaen-3-yl]acetate.

Workup

  1. temperaturerefluxed for 2 h
  2. temperatureThen, cooled
  3. concentrationconcentrated
  4. customthe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-65e5e40f480142598284475a782f6b6e
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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