Diisopropylethylamine → HCID 67051709, compound

HRID 605757Notes

Reaction equation

HRID 605757 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([CH:20]=[CH:21][N:22]=2)[CH:5]=[C:6]([C:17]([OH:19])=O)[C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16].C(N(CC)C(C)C)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.[N+:66]([CH:69]([C:71]1([OH:75])[CH2:74][NH:73][CH2:72]1)[CH3:70])([O-:68])=[O:67]>CN(C)C=O>[Cl:1][C:2]1[C:3]2[N:4]([CH:20]=[CH:21][N:22]=2)[CH:5]=[C:6]([C:17]([N:73]2[CH2:74][C:71]([CH:69]([N+:66]([O-:68])=[O:67])[CH3:70])([OH:75])[CH2:72]2)=[O:19])[C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 211115608-Chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridine-6-carboxylic acidHCID 67051866HCID 67051866, compound

Product 1

HCID 67051709HCID 67051709, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridine-6-carboxylic acid (150 mg, 0.35 mmol) (prepared using procedures similar to those described in US 2006030610 and US 2005054701), N,N-diisopropylethylamine (300 μL, 1.74 mmol), PyBOP (180 mg, 0.35 mmol) and 3-(1-nitroethyl)azetidin-3-ol hydrochloride (76 mg, 0.42 mmol) in dimethylformamide (3 mL) was stirred at room temperature for 15 hours. The reaction mixture was then partitioned between 5% aqueous lithium chloride, and ethyl acetate. The aqueous portion was extracted twice using ethyl acetate. The combined organic portion was washed with 20% aqueous citric acid, brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown residue which was purified by column chromatography. Eluting with 5% methanol in dichloromethane, the isolated product was concentrated in vacuo to afford 195 mg, 0.35 mmol (100%) of 1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}carbonyl)-3-(1-nitro ethyl)azetidin-3-ol as a yellow foam. 1H NMR (400 MHz, CDCl3): 8.28 (s, 1H), 7.68 (s, 1H), 7.59 (s, 1H), 7.43 (d, 1H), 7.31 (d, 1H), 7.23 (br s, 1H), 6.55-6.51 (m, 1H), 6.02 (br s, 1H), 4.79 (q, 1H), 4.45-3.96 (4H), 1.56 (d, 3H). MS (EI) for C20H19ClFI6O4: 560 (MH+).

Workup

  1. customThe reaction mixture was then partitioned between 5% aqueous lithium chloride, and ethyl acetate
  2. extractionThe aqueous portion was extracted twice using ethyl acetate
  3. washThe combined organic portion was washed with 20% aqueous citric acid, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a brown residue which
  8. customwas purified by column chromatography
  9. washEluting with 5% methanol in dichloromethane
  10. concentrationthe isolated product was concentrated in vacuo

Sources & evidence

ORD record
ord-3af04422777146159695acd8bfe641e9
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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