4-[6-(6-Chloro-pyridin-3-ylamino)-5-cyano-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester → 4-[5-Cyano-6-(6-propyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 2377895Notes

Reaction equation

HRID 2377895 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([C:20]#[N:21])=[C:18]([NH:22][C:23]3[CH:24]=[N:25][C:26](Cl)=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[Br-].[CH2:31]([Zn+])[CH2:32][CH3:33]>C1(P([Pd](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1COCC1>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([C:20]#[N:21])=[C:18]([NH:22][C:23]3[CH:24]=[N:25][C:26]([CH2:31][CH2:32][CH3:33])=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 865973614-[6-(6-Chloro-pyridin-3-ylamino)-5-cyano-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl esterHCID 178455869HCID 178455869, compound

Product 1

HCID 598568294-[5-Cyano-6-(6-propyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

Reagents, catalysts & solvents 2

HCID 178420554HCID 178420554, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a 25 mL round-bottomed flask fitted with a condenser and N2 inlet was placed 4-[6-(6-chloro-pyridin-3-ylamino)-5-cyano-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (100 mg, 1.3 mmol), n-propylzinc bromide (0.5M in THF, 0.72 mL), tetrakis (triphenylphosphino)palladium (28 mg, 0.024 mmol), and THF (3.5 mL). The reaction mixture was refluxed overnight under N2 atmosphere. The product was purified by preparative HPLC. 1H NMR (CDCl3, 400 MHz) δ 1.03 (t, 3H), 1.26 (d, 6H), 1.85 (m, 4H), 1.98 (m, 2H), 3.04 (t, 2H), 3.44 (m, 2H), 3.77 (m, 2H), 4.94 (m, 1H), 5.46 (m, 1H), 7.57 (d, 1H), 8.34 (s, 1H), 8.51 (s, 1H), 8.56 (d, 1H), 9.42 (s, 1H). Exact mass calculated for C22H28N6O3 424.22, found 425.2 (MH+).

Workup

  1. customIn a 25 mL round-bottomed flask fitted with a condenser and N2 inlet
  2. temperatureThe reaction mixture was refluxed overnight under N2 atmosphere
  3. customThe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-59ee66e50a1142448fa7983c1516bc5b
Source dataset
uspto-grants-2008_12
Patent number
US07470699B2

Reaction notes

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