1,4-Dioxane → HCID 117739998, compound

HRID 1775894Notes

Reaction equation

HRID 1775894 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.O.O.O.O.O.O.O.O.O.O.C(=O)([O-])[O-].[Na+].[Na+].Br[C:28]1[CH:29]=[N:30][C:31]([C:34]2[CH:39]=[CH:38][C:37]([CH2:40][C@H:41]([NH:65][C:66]([C:68]3[S:69][C:70]([C:73]([CH3:76])([CH3:75])[CH3:74])=[CH:71][CH:72]=3)=[O:67])[C:42]([NH:44][CH:45]([CH:53]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])[C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])=[O:43])=[CH:36][CH:35]=2)=[N:32][CH:33]=1.O1CCOCC1>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].O>[C:61]([O:60][CH:53]([C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)[CH:45]([NH:44][C:42](=[O:43])[C@@H:41]([NH:65][C:66]([C:68]1[S:69][C:70]([C:73]([CH3:75])([CH3:74])[CH3:76])=[CH:71][CH:72]=1)=[O:67])[CH2:40][C:37]1[CH:38]=[CH:39][C:34]([C:31]2[N:30]=[CH:29][C:28]([C:5]3[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=3)=[CH:33][N:32]=2)=[CH:35][CH:36]=1)[C:46]([O:48][C:49]([CH3:52])([CH3:50])[CH3:51])=[O:47])([CH3:62])([CH3:63])[CH3:64]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 151402Sodium Carbonate DecahydrateHCID 27343604-Hydroxyphenylboronic acidHCID 117740151HCID 117740151, compound

Product 1

HCID 117739998HCID 117739998, compoundYield 106%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a 100 ml flask were added (4-hydroxyphenyl)boronic acid (63 mg, 0.5 mmol), sodium carbonate decahydrate (217 mg, 0.8 mmol), tert-butyl 2-((S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)propanamido)-3-(tert-butoxy)-3-phenylpropanoate (290 mg, 0.4 mmol), Pd(dppf)Cl2 (28 mg, 0.04 mmol), dioxane (10.0 mL), and water (2.0 mL). The reaction mixture was heated to 80° C. overnight. The reaction mixture was dried under reduced pressure to remove the solvent and diluted in DCM (20 mL). The mixture was washed with aqueous NaHCO3 (3×10 mL). The combined organics were dried over Na2SO4 and evaporated to afford 309 mg (106%) of crude tert-butyl 3-(tert-butoxy)-2-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-hydroxyphenyl)pyrimidin-2-yl)phenyl)propanamido)-3-phenylpropanoate INT-51 which was used without further purification. LCMS-ESI (m/z) calculated for C45H52N4O6S: 776.9. found 721 [M−tBuO]+, tR=11.03 min. (Method 14).

Workup

  1. customThe reaction mixture was dried under reduced pressure
  2. customto remove the solvent
  3. additiondiluted in DCM (20 mL)
  4. washThe mixture was washed with aqueous NaHCO3 (3×10 mL)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-432b8752589d437088a5f982d762fdd9
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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