Sodium Carbonate → 2-Amino-5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)-pyrimidin-4-yl]-isonicotinonitrile

HRID 1043805Notes

Reaction equation

HRID 1043805 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]#[N:9])[C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Br[C:20]1[N:25]=[C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:23]=[C:22]([NH:32][C:33]2[CH:34]=[N:35][C:36]3[C:41]([CH:42]=2)=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[NH2:1][C:2]1[CH:7]=[C:6]([C:5]([C:20]2[CH:21]=[C:22]([NH:32][C:33]3[CH:34]=[N:35][C:36]4[C:41]([CH:42]=3)=[CH:40][CH:39]=[CH:38][CH:37]=4)[N:23]=[C:24]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:25]=2)=[CH:4][N:3]=1)[C:8]#[N:9]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 595075092-Amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-4-carbonitrileHCID 59507540N-(6-bromo-2-morpholinopyrimidin-4-yl)quinolin-3-amine

Product 1

HCID 595077342-Amino-5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)-pyrimidin-4-yl]-isonicotinonitrileYield 20.7%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To the crude 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-4-carbonitrile (prepared as in Method 11) (25 mg, 0.13 mmol) solution in dioxane (1.8 mL) in a pressure vessel, was added (6-bromo-2-morpholin-4-yl-pyrimidin-4-yl)-quinolin-3-yl-amine (19.4 mg, 0.05 mmol) and aq. Na2CO3 (2 M, 0.6 mL, 1.2 mmol). After purging the reaction mixture with argon, dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (10.3 mg, 0.01 mmol) was added in one portion. The pressure vessel was sealed and the mixture was heated in a microwave at 120° C. for 900 seconds. The crude mixture was filtered and concentrated under reduced pressure. The crude product was purified by reverse phase preparative HPLC to give 2-amino-5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)-pyrimidin-4-yl]-isonicotinonitrile (4.4 mg, 20%). LC/MS (m/z): 425.0 (MH+), Rt 2.03 minutes.

Workup

  1. additionwas added in one portion
  2. customThe pressure vessel was sealed
  3. filtrationThe crude mixture was filtered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-cd27fb8b05aa4e9a8e04d7eccda4faa2
Source dataset
uspto-grants-2013_10
Patent number
US08563549B2

Reaction notes

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