1,2-Dichloroethane → HCID 10282444, compound

HRID 397531Notes

Reaction equation

HRID 397531 reaction equation
[Cl:1][C:2]1[C:3]([CH2:21][C:22]([OH:24])=O)=[C:4]([F:20])[C:5]([NH:8][CH2:9][C:10]([F:19])([F:18])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N+:12]=2[O-])=[N:6][CH:7]=1.[NH2:25][CH2:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[CH2:34][CH2:35][NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[Cl:33][C:31]1[CH:30]=[CH:29][C:28]([CH2:34][CH2:35][NH:36][C:37](=[O:43])[O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[C:27]([CH2:26][NH:25][C:22](=[O:24])[CH2:21][C:3]2[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([NH:8][CH2:9][C:10]([F:18])([F:19])[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[C:4]=2[F:20])[CH:32]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 23000557HCID 23000557, compoundHCID 23000581HCID 23000581, compound

Product 1

HCID 10282444HCID 10282444, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.035 g (0.1 mmol) (5-chloro-2-{[2,2-difluoro-2-(2-pyridinyl)ethyl]amino}-3-fluoro-4-pyridinyl)acetic acid 1-9 (mixed with LiCl) in 1 mL DMF was added 0.029 g (0.1 mmol) tert-butyl 2-[2-(aminomethyl)-4-chlorophenyl]ethylcarbamate, 0.03 g (0.15 mmol) EDC and 0.014 g (0.1 mmol) HOAt and the reaction mixture stirred at room temperature 4 h, then diluted with 50 mL EtOAc, washed with 50 mL saturated aqueous sodium bicarbonate solution, brine, then dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography (2×12 cm silica gel, linear gradient 2-6% MeOH (containing 10% saturated ammonium hydroxide solution)/CH2Cl2 afforded tert-butyl 2-[4-chloro-2-({[(5-chloro-2-{[2,2-difluoro-2-(2-pyridinyl)ethyl]amino}-3-fluoro-4-pyridinyl)acetyl]amino}methyl)phenyl]ethylcarbamate 1-10. 1H NMR (400 mHz, CD3OD) δ8.60 (d, 1H, J=4.58 Hz); 7.89 (ddd, J=7.7, 7.7, and 1.47 Hz); 7.72 (s, 1H); 7.67 (d, 1H, J=7.87 Hz); 7.46 (dd, 1H, J=7.51 and 4.58); 7.29(d, 1H, J=1.83 Hz); 7.18 (m, 2H); 4.42 (s, 2H); 4.32 (t, 2H, J=13.9 Hz); 3.74 (d, 2H, J=1.46 Hz); 3.21 (t, 2H, J=7.14 Hz); 2.80 (t, 2H, J=7.4 Hz); 1.40 (s, 9H). Mass Spectrum (electrospray) M+H=612.3.

Workup

  1. washwashed with 50 mL saturated aqueous sodium bicarbonate solution, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography (2×12 cm silica gel, linear gradient 2-6% MeOH (containing 10% saturated ammonium hydroxide solution)/CH2Cl2

Sources & evidence

ORD record
ord-69fa4a68de55472b8a5798c6fb7253ed
Source dataset
uspto-grants-2003_08
Patent number
US06610701B2

Reaction notes

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