Water → HCID 67437248, compound

HRID 521375Notes

Reaction equation

HRID 521375 reaction equation
C([O-])([O-])=O.[Na+].[Na+].Cl[C:8]1[C:9]2[C@H:16]([CH3:17])[CH2:15][CH2:14][C:10]=2[N:11]=[CH:12][N:13]=1.[CH3:18][O:19][C:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)=[O:21].O>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]>[CH3:17][C@H:16]1[C:9]2[C:8]([C:25]3[CH:26]=[CH:27][C:22]([C:20]([O:19][CH3:18])=[O:21])=[CH:23][CH:24]=3)=[N:13][CH:12]=[N:11][C:10]=2[CH2:14][CH2:15]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Product 1

HCID 67437248HCID 67437248, compoundYield 74.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of Na2CO3 (1.65 mL, 1M) was added to a solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (253 mg, 1.50 mmol) and 4-methoxycarbonylphenylboronic acid (297 mg, 1.65 mmol) in 1,4-dioxane (4.5 mL). The mixture was sparged with N2 for 2 minutes. The catalyst Pd(dppf)Cl2 (98 mg, 0.12 mmol) was added in one portion. The reaction vial was sealed and heated in microwave to 110° C. for 30 minutes. Water (20 mL) was added to the mixture and extracted with DCM (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (0-50% EtOAc/hexane gradient elution) to give (R)-methyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)benzoate as an oil (300 mg, 70%). 1H NMR (CDCl3, 500 MHz) δ 9.07 (s, 1H), 8.16 (d, =8.5 Hz, 2H), 7.88 (d, J=8.5 Hz, 2H), 3.96 (s, 3H), 3.81-3.76 (m, 1H), 3.15-3.00 (m, 2H), 2.44-2.40 (m, 1H), 1.78-1.74 (m, 1H), 1.01 (d, J=6.5 Hz, 3H).

Workup

  1. customThe mixture was sparged with N2 for 2 minutes
  2. customThe reaction
  3. customvial was sealed
  4. extractionextracted with DCM (3×15 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0-50% EtOAc/hexane gradient elution)

Sources & evidence

ORD record
ord-a50bc6295879432eb1878be6ac7bd5b8
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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