Water → (R)-tert-butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 521382Notes

Reaction equation

HRID 521382 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.B1([C:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH:28]=2)OC(C)(C)C(C)(C)O1.O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:17][C@H:16]1[C:9]2[C:8]([C:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH:28]=3)=[N:13][CH:12]=[N:11][C:10]=2[CH2:14][CH2:15]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Product 1

HCID 67438528(R)-tert-butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of Na2CO3 (0.36 mL, 2M) was added to a solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (101 mg, 0.60 mmol), 3,6-dihydro-2H-pyridine-1-tert-butoxycarbonyl-4-boronic acid, pinacol ester (204 mg, 0.66 mmol) in 1,4-dioxane (1.8 mL). The mixture was sparged with N2 for 2 minutes. The catalyst Pd(PPh3)2Cl2 (21 mg, 0.03 mmol) was added in one portion. The mixture was heated at 110° C. under N2 for 8 hours. 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 (first with 0-50% EtOAc/hexane, then with 0-4% MeOH/DCM gradient elution) to give (R)-tert-butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate as an oil (127 mg, 67%). 1H NMR (CDCl3, 500 MHz) δ 8.91 (s, 1H), 6.31 (s, 1H), 3.64-3.55 (m, 1H), 3.10-3.03 (m, 2H), 2.98-2.90 (m, 2H), 2.83-2.78 (m, 1H), 2.42-2.34 (m, 2H), 1.77-1.69 (m, 2H), 1.49 (s, 9H), 1.19 (d, J=7.0 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-97c2aa2aa7834e919f72681b9e40d2f0
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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