Cesium carbonate → HCID 136377184, compound

HRID 1027304Notes

Reaction equation

HRID 1027304 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[N:12][C:11]([N:14]3[CH2:18][C@@H:17]4[CH2:19][N:20](C(OC(C)(C)C)=O)[CH2:21][C@@H:16]4[CH2:15]3)=[CH:10][CH:9]=2)=[C:4]([OH:29])[CH:3]=1.CC1(C)C(C)(C)OB([C:38]2[CH:39]=[N:40][N:41](C(OC(C)(C)C)=O)[CH:42]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>CC(C1C=C(C(C)C)C(C2C(OC)=CC(Cl)=C(OC)C=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.[Pd+2].O>[CH2:15]1[C@@H:16]2[CH2:21][NH:20][CH2:19][C@@H:17]2[CH2:18][N:14]1[C:11]1[N:12]=[N:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:38]3[CH:39]=[N:40][NH:41][CH:42]=3)=[CH:3][C:4]=2[OH:29])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 136377183HCID 136377183, compound

Product 1

HCID 136377184HCID 136377184, compoundYield 51.3%

Reagents, catalysts & solvents 2

HCID 75412134Dicyclohexyl(2 inverted exclamation mark,4 inverted exclamation mark,6 inverted exclamation mark-Triisopropyl-3,6-Dimethoxy-[1,1 inverted exclamation mark-Biphenyl]-2-Yl)Phosphine-(2-(2-Aminoethyl)Phenyl)Palladium(Ii) ChlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a 10 mL microwave vial, was added (3aR,6aS)-tert-butyl 5-(6-(4-chloro-2-hydroxyphenyl)pyridazin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (0.182 g, 0.437 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.385 g, 1.310 mmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (0.035 g, 0.044 mmol) and Cs2CO3 (0.427 g, 1.310 mmol), followed by adding 1,4-dioxane (2 mL) and water (0.5 mL). The reaction mixture was evacuated and filled with N2 twice then heated at 90° C. overnight. The reaction mixture was filtered through celite and washed with DMSO and MeOH. The filtrate was acidified with 1N HCl and stirred at RT for 3 hour, then extracted with DCM. The aqueous layer was basified with 2M NH2 in MeOH and a brownish precipitate formed, which was filtered and washed with DMSO to afford a grey solid 2-(6-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol (82 mg, 0.224 mmol, 51.2% yield). MS (M+1)=349.1. The DMSO wash solution was concentrated to afford a DMSO solution of desired (3aR,6aS)-tert-butyl 5-(6-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (75 mg, 0.167 mmol, 38% yield), MS (M+1)=449.1, which was used directly in the next step.

Workup

  1. customThe reaction mixture was evacuated
  2. additionfilled with N2 twice
  3. filtrationThe reaction mixture was filtered through celite
  4. washwashed with DMSO and MeOH
  5. extractionextracted with DCM
  6. customa brownish precipitate formed
  7. filtrationwhich was filtered
  8. washwashed with DMSO

Sources & evidence

ORD record
ord-9acbf1474aaa4c33b9c0c05ea553976e
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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