Sodium Carbonate → 2-Amino-3-{4-[6-(3-cyclopentyloxy-4-methoxy-benzylamino)-pyrimidin-4-yl]-phenyl}-propionic acid

HRID 254751Notes

Reaction equation

HRID 254751 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:11]=2)[CH:3]=1.B([C:27]1[CH:38]=[CH:37][C:30]([CH2:31][C@@H:32]([C:34]([OH:36])=[O:35])[NH2:33])=[CH:29][CH:28]=1)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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.C(#N)C>[NH2:33][CH:32]([CH2:31][C:30]1[CH:37]=[CH:38][C:27]([C:2]2[CH:3]=[C:4]([NH:8][CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)[CH:11]=3)[N:5]=[CH:6][N:7]=2)=[CH:28][CH:29]=1)[C:34]([OH:36])=[O:35]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 150315L-p-BoronophenylalanineHCID 86614298(6-Chloro-pyrimidin-4-yl)-(3-cyclopentyloxy-4-methoxy-benzyl)-amine

Product 1

HCID 666494062-Amino-3-{4-[6-(3-cyclopentyloxy-4-methoxy-benzylamino)-pyrimidin-4-yl]-phenyl}-propionic acidYield 6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

An Emrys process vial (2-5 ml) for microwave was charged with (6-chloro-pyrimidin-4-yl)-(3-cyclopentyloxy-4-methoxy-benzyl)-amine (64 mg, 0.19 mmol), 4-borono-L-phenylalanine (40 mg, 0.19 mmol) and 2 ml of acetonitrile. Aqueous sodium carbonate (2 ml, 1M) was added to above solution followed by 5 mol percent of dichlorobis-(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated to 150° C. for 5 minutes with microwave. After cooling, the reaction mixture was evaporated to dryness. The residue was dissolved in 2.5 ml of methanol and purified with Prep-LC to give 5.3 mg of 2-amino-3-{4-[6-(3-cyclopentyloxy-4-methoxy-benzylamino)-pyrimidin-4-yl]-phenyl}-propionic acid, yield 6%. 1H-NMR (400 MHz, DMSO-d6): δ 1.46 (m, 2H), 1.62 (m, 4H), 3.01 (m, 2H), 3.08 (m, 2H), 3.65 (s, 3H), 4.20 (m, 1H), 4.46 (d, 2H), 4.68 (m, 1H), 6.82 (t, 2H), 6.87 (d, 2H), 7.40 (d, 2H), 7.90 (s, 2H), 8.25 (s, 2H), 8.6 (s, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling
  3. customthe reaction mixture was evaporated to dryness
  4. dissolutionThe residue was dissolved in 2.5 ml of methanol
  5. custompurified with Prep-LC

Sources & evidence

ORD record
ord-15fc9364beba4b258959d8024564e5dc
Source dataset
uspto-grants-2011_01
Patent number
US07875622B2

Reaction notes

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