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Dichloromethane → ethyl ((1S)-5-{3-[[2,5-bis(4-methoxyphenyl)-4-pyrimidinyl](methy)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603495
Notes
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Reaction equation

HRID 603495 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Cl[C:13]1[N:18]=[C:17]([N:19]([CH3:39])[CH2:20][CH2:21][CH2:22][O:23][C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[C@H:29]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:28][CH2:27]3)[C:16](Cl)=[CH:15][N:14]=1.C(Cl)Cl.[C:44](=[O:47])([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=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]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:13]2[N:18]=[C:17]([N:19]([CH3:39])[CH2:20][CH2:21][CH2:22][O:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[C@H:29]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:28][CH2:27]4)[C:16]([C:3]3[CH:8]=[CH:7][C:6]([O:47][CH3:44])=[CH:5][CH:4]=3)=[CH:15][N:14]=2)=[CH:5][CH:4]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 59300554ethyl ((1S)-5-{3-[(2,5-dichloro-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300448ethyl ((1S)-5-{3-[[2,5-bis(4-methoxyphenyl)-4-pyrimidinyl](methy)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate
Yield 64.8%

Reagents, catalysts & solvents 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 4-methoxyphenylboronic acid (142 mg, 0.913 mmol) and ethyl ((1S)-5-{3-[(2,5-dichloro-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 442, 100 mg, 0.228 mmol) in toluene (5 mL) and 1,4-dioxane (1.25 mL) was added PdCl2(dppf).CH2Cl2 (19 mg, 0.023 mmol). The mixture was purged with argon for 15 min after which sodium carbonate (1.2 mL, 2.40 mmol, 2 M aqueous solution) was added. The mixture was stirred at 75° C. for 18 h, cooled to rt, and then washed with a saturated sodium bicarbonate solution. The organic layer was separated from the mixture and the aqueous phase extracted with EtOAc. The combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (1:4 EtOAc/Hexanes) to give (86 mg, 64%) of the desired product. 1H NMR (400 MHz, CDCl3): δ 1.30 (t, 3H), 1.70-1.80 (m, 1H), 2.15-2.20 (m, 2H), 2.28-2.45 (m, 2H), 2.70 (dd, 1H), 2.72-2.90 (m, 2H), 2.80 (s, 3H), 3.45-3.55 (m, 1H), 3.75 (t, 2H), 3.85 (s, 3H), 3.92 (s, 3H), 3.95 (t, 2H), 4.20 (q, 2H), 6.65 (d, 1H), 6.7 (s, 1H), 6.9 (d, 2H), 6.95 (d, 2H), 7.05 (s, 1H), 7.32 (d, 2H), 8.15 (s, 1H), 8.40 (d, 2H).

Workup

  1. additionwas added
  2. temperaturecooled to rt
  3. washwashed with a saturated sodium bicarbonate solution
  4. customThe organic layer was separated from the mixture
  5. extractionthe aqueous phase extracted with EtOAc
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography (1:4 EtOAc/Hexanes)

Sources & evidence

ORD record
ord-3343ab79b3984e05b3190803ecfe57ab
Source dataset
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07906653B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes