Triethylamine → 1-(4-(6-(2-Amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one

HRID 401473Notes

Reaction equation

HRID 401473 reaction equation
[N:1]1([C:8]2[N:13]=[C:12]([C:14]([C:16]3[C:17]([NH2:23])=[N:18][CH:19]=[C:20]([Br:22])[CH:21]=3)=[O:15])[CH:11]=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[F:24][C:25]([F:31])([F:30])[CH2:26][C:27](O)=[O:28].ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.N=C=N>ClCCl>[NH2:23][C:17]1[N:18]=[CH:19][C:20]([Br:22])=[CH:21][C:16]=1[C:14]([C:12]1[N:13]=[C:8]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([C:27](=[O:28])[CH2:26][C:25]([F:31])([F:30])[F:24])[CH2:3][CH2:2]2)[CH:9]=[CH:10][CH:11]=1)=[O:15]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 27779723,3,3-Trifluoropropionic acidHCID 24871523(6-(1,4-Diazepan-1-yl)pyridin-2-yl)(2-amino-5-bromopyridin-3-yl)methanone

Product 1

HCID 249928341-(4-(6-(2-Amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-oneYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(6-(1,4-diazepan-1-yl)pyridin-2-yl)(2-amino-5-bromopyridin-3-yl)methanone (650 mg, 1.36 mmol) was added to a stirred suspension of 3,3,3-trifluoropropionic acid (0.13 ml, 1.50 mmol), 1-hydroxybenzotriazole (184 mg, 1.36 mmol), triethylamine (1.33 ml, 9.52 mmol) and PS-carbodiimide (2.08 g, 2.72 mmol) in dichloromethane (20 ml). The resulting mixture was stirred at room temperature for 18 hours. The crude mixture was filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion|, 40 g column, 0-50% EtOAc/Petroleum ether) to afford the title compound as an orange solid (355 mg, 54% yield).

Workup

  1. filtrationThe crude mixture was filtered
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified on silica gel by flash column chromatography (ISCO Companion|, 40 g column, 0-50% EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-8aafd9f3630648cea2c5172316fbf40a
Source dataset
uspto-grants-2014_06
Patent number
US08741931B2

Reaction notes

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