Sodium Carbonate → 1-(4-(6-(2-Amino-5-vinylnicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one

HRID 401474Notes

Reaction equation

HRID 401474 reaction equation
[NH2:1][C:2]1[N:29]=[CH:28][C:27](Br)=[CH:26][C:3]=1[C:4]([C:6]1[N:11]=[C:10]([N:12]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:25])[CH2:20][C:21]([F:24])([F:23])[F:22])[CH2:14][CH2:13]2)[CH:9]=[CH:8][CH:7]=1)=[O:5].[CH:31](B1OC(C)(C)C(C)(C)O1)=[CH2:32].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1(C)C=CC=CC=1.C1C=CC([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)=CC=1>[NH2:1][C:2]1[N:29]=[CH:28][C:27]([CH:31]=[CH2:32])=[CH:26][C:3]=1[C:4]([C:6]1[N:11]=[C:10]([N:12]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:25])[CH2:20][C:21]([F:24])([F:23])[F:22])[CH2:14][CH2:13]2)[CH:9]=[CH:8][CH:7]=1)=[O:5]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 249928341-(4-(6-(2-Amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one

Product 1

HCID 576907361-(4-(6-(2-Amino-5-vinylnicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-oneYield 21.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of 1-(4-(6-(2-amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one (355 mg, 0.73 mmol), vinyl boronic acid pinacol ester (0.15 ml, 0.88 mmol), tetrakis(triphenylphosphine)palladium(0) (42 mg) and a 2M aqueous solution of sodium carbonate (2 ml) in ethanol (1 ml) and toluene (3 ml) was heated under microwave irradiation at 110° C. for 5 hours. The reaction mixture was concentrated in vacuo. The residue was slurried in ethyl acetate, filtered to remove the inorganic salts and concentrated to dryness in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as an orange solid (68 mg, 21% yield).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. filtrationfiltered
  3. customto remove the inorganic salts
  4. concentrationconcentrated to dryness in vacuo
  5. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  6. customThe fractions were collected
  7. customfreeze-dried

Sources & evidence

ORD record
ord-09572afee1f64a46b7683120c893701a
Source dataset
uspto-grants-2014_06
Patent number
US08741931B2

Reaction notes

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