Sodium Carbonate → HCID 58464904, compound

HRID 1185412Notes

Reaction equation

HRID 1185412 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-a7f0263102ca4f9dbc6f7159d4082cac
Source dataset
uspto-grants-2014_03
Patent number
US08669361B2

Reaction notes

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