Sodium Carbonate → HCID 58464904, compound

HRID 2089456Notes

Reaction equation

HRID 2089456 reaction equation
N[C:2]1SC(C2C=CC=C(Br)C=2F)=N[C:3]=1C(NC1C=NN(C)C=1N1CCC[C@@H](N)CC1)=O.[CH2:32]([O:39][C:40]([NH:42][C@@H:43]1[CH2:49][CH2:48][CH2:47][N:46]([C:50]2[N:54]([CH3:55])[N:53]=[CH:52][C:51]=2[NH:56][C:57]([C:59]2[N:60]=[C:61]([C:72]3[CH:77]=[CH:76][CH:75]=[C:74](Br)[C:73]=3[F:79])[S:62][C:63]=2[NH:64][C:65](=[O:71])[O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:58])[CH2:45][CH2:44]1)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CC1(C)C(C)(C)OB(C=C)O1.C([O-])([O-])=O.[Na+].[Na+].C([O-])(=O)C.[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[CH2:32]([O:39][C:40]([NH:42][C@@H:43]1[CH2:49][CH2:48][CH2:47][N:46]([C:50]2[N:54]([CH3:55])[N:53]=[CH:52][C:51]=2[NH:56][C:57]([C:59]2[N:60]=[C:61]([C:72]3[CH:77]=[CH:76][CH:75]=[C:74]([CH:2]=[CH2:3])[C:73]=3[F:79])[S:62][C:63]=2[NH:64][C:65](=[O:71])[O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:58])[CH2:45][CH2:44]1)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 58464876HCID 58464876, compoundHCID 58464936HCID 58464936, compound

Product 1

HCID 58464904HCID 58464904, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Procedure

The Boc and Cbz protected intermediate of compound 373 from Example 373, tert-butyl N-[4-[[5-[(4R)-4-(benzyloxycarbonylamino)azepan-1-yl]-1-methyl-pyrazol-4-yl]carbamoyl]-2-(3-bromo-2-fluoro-phenyl)thiazol-5-yl]carbamate, (158 mg; 0.213 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (98 mg, 0.11 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (16 mg, 0.021 mmol), a 1M solution of Na2CO3 (0.32 mL), a 1M solution of potassium acetate (0.32 mL) and acetonitrile (3.5 mL) were charged in a microwave reaction vial. The mixture was irradiated to 130° C. with a microwave for 30 min and cooled to room temperature. It was filtered through Celite and thoroughly washed with methanol. The filtrate was concentrated and the residue was purified via flash chromatography, 0 to 100% ethyl acetate in heptane to give tert-butyl N-[4-[[5-[(4R)-4-(benzyloxycarbonylamino)azepan-1-yl]-1-methyl-pyrazol-4-yl]carbamoyl]-2-(2-fluoro-3-vinyl-phenyl)thiazol-5-yl]carbamate.

Workup

  1. customThe mixture was irradiated to 130° C. with a microwave for 30 min
  2. filtrationIt was filtered through Celite
  3. washthoroughly washed with methanol
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified via flash chromatography, 0 to 100% ethyl acetate in heptane

Sources & evidence

ORD record
ord-a043a05efb414af28046249745d28747
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

Loading…