Sodium t-butoxide → HCID 178503401, compound

HRID 707262Notes

Reaction equation

HRID 707262 reaction equation
Cl[C:2]1[C:7]([C:8]([CH3:15])([CH3:14])[C:9]([O:11]CC)=O)=[CH:6][N:5]=[C:4]([S:16][CH3:17])[N:3]=1.[C:18]([O:22][C:23](=[O:30])[NH:24][C@H:25]1[CH2:28][C@H:27]([NH2:29])[CH2:26]1)([CH3:21])([CH3:20])[CH3:19].C1(P(C2CCCCC2)C2C(OC)=CC=C(OC)C=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:18]([O:22][C:23](=[O:30])[NH:24][C@H:25]1[CH2:28][C@H:27]([N:29]2[C:2]3[N:3]=[C:4]([S:16][CH3:17])[N:5]=[CH:6][C:7]=3[C:8]([CH3:14])([CH3:15])[C:9]2=[O:11])[CH2:26]1)([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 25112535BrettphosHCID 86694234Ethyl 2-(4-chloro-2-(methylthio)pyrimidin-5-yl)-2-methylpropanoateHCID 178454111HCID 178454111, compound

Product 1

HCID 178503401HCID 178503401, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial containing a mixture of ethyl 2-(4-chloro-2-(methylthio)pyrimidin-5-yl)-2-methylpropanoate (2.08 g, 7.57 mmol), tert-butyl(trans-3-aminocyclobutyl)carbamate (1.551 g, 8.33 mmol), tris(dibenzylideneacetone) dipalladium (0) (0.520 g, 0.568 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (0.731 g, 1.363 mmol) and sodium tert-butoxide (2.317 ml, 18.93 mmol) in dioxane (15 mL) was purged with argon and capped. The reaction mixture was heated at 100° C. for 3 hours, cooled, and partitioned between water (200 mL) and ethyl actate (200 mL). The organic was isolated and concentrated under reduced pressure. Purification using the ISCO eluting with 0-70% EtOAc/hexane to give the desired product tert-butyl(trans-3-(5,5-dimethyl-2-(methylthio)-6-oxo-5H-pyrrolo[2,3-d]pyrimidin-7(6H)-yl)cyclobutyl)carbamate (0.9 g, 2.378 mmol, 31.4% yield). m/z: 379.2 (M+1).

Workup

  1. additionA microwave vial containing
  2. customwas purged with argon
  3. customcapped
  4. temperaturecooled
  5. custompartitioned between water (200 mL) and ethyl actate (200 mL)
  6. customThe organic was isolated
  7. concentrationconcentrated under reduced pressure
  8. customPurification
  9. washeluting with 0-70% EtOAc/hexane

Sources & evidence

ORD record
ord-8331d7a0352548eda94aba5b49ba6ad2
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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