(2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(2'-(allyloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate → methyl (2S)-2-(4-methyl-21,29-dioxa-5,7,8-triazaheptacyclo[24.6.2.16,9.110,14.02,7.015,20.030,34]hexatriaconta-1(33),2,4,6(36),8,10,12,14(35),15,17,19,23,30(34),31-tetradecaen-3-yl)-2-[(2-methylpropan-2-yl)oxy]acetate

HRID 1400717Notes

Reaction equation

HRID 1400717 reaction equation
[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=6[O:35][CH2:36]C=C)[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:39])[C:15]=3[C@H:40]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[C:41]([O:43][CH3:44])=[O:42])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3]>ClCCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C(OC(C)C)=CC=CC=3)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:46]([O:45][C@@H:40]([C:15]1[C:16]([CH3:39])=[N:17][C:18]2=[CH:22][C:21]3=[N:20][N:19]2[C:14]=1[C:11]1[CH:12]=[C:13]2[C:8]([O:7][CH2:6][CH2:5][CH:4]2[CH2:1][CH:2]=[CH:3][CH2:36][O:35][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[C:25]2[CH:24]=[C:23]3[CH:28]=[CH:27][CH:26]=2)=[CH:9][CH:10]=1)[C:41]([O:43][CH3:44])=[O:42])([CH3:47])([CH3:48])[CH3:49]

Participants

4

Reactant 1

HCID 89971576(2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(2'-(allyloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 123838531methyl (2S)-2-(4-methyl-21,29-dioxa-5,7,8-triazaheptacyclo[24.6.2.16,9.110,14.02,7.015,20.030,34]hexatriaconta-1(33),2,4,6(36),8,10,12,14(35),15,17,19,23,30(34),31-tetradecaen-3-yl)-2-[(2-methylpropan-2-yl)oxy]acetateYield 84%

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

A solution of (2S)-methyl 2-(7-(4-allylchroman-6-yl)-2-(2′-(allyloxy)-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.373 g, 0.567 mmol) in DCE (275 ml) was heated (70° C.) and then treated with Hoveyda-Grubbs cat.2nd gen. (0.025 g, 0.040 mmol). The reaction was stirred for 2.5 hrs, then additional catalyst (0.025 g, 0.040 mmol) was added, the temperature was raised (80° C.) and the reaction was stirred for 30 min. The reaction was cooled, concentrated, and the residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes) to afford the desired product (0.300 g, 0.476 mmol, 84% yield). LCMS (M+H)=630.5.

Workup

  1. stirringthe reaction was stirred for 30 min
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. customthe residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes)

Sources & evidence

ORD record
ord-b9a1f1746800436b9561985405180da7
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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