1,2-Dichloroethane → HCID 86731023, compound

HRID 1852488Notes

Reaction equation

HRID 1852488 reaction equation
[C:1]([C:4]1[C:5]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:6][N:7]([CH:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=[O:16])[CH2:11][CH:10]2[C:18]#[N:19])[CH:8]=1)(=[O:3])[NH2:2].[CH2:28](Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CO>[C:1]([C:4]1[C:5]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)=[N:6][N:7]([CH:9]2[CH2:14][CH2:13][CH:12]([C:15]([O:17][CH3:28])=[O:16])[CH2:11][CH:10]2[C:18]#[N:19])[CH:8]=1)(=[O:3])[NH2:2]

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 86731022HCID 86731022, compound

Product 1

HCID 86731023HCID 86731023, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the crude acid (1S,3S,4S and 1R,3R,4R)-4-[4-carbamoyl-3-[(4-chlorophenyl)amino]-1H-pyrazol-1-yl]-3-cyanocyclohexane-1-carboxylic acid (Example #35-1 Step C, 500 mg, 1.3 mmol) in MeOH (5 mL) were sequentially added EDC (324 mg, 1.7 mmol) and HOBt (210 mg, 1.6 mmol). The resulting solution was stirred at ambient temperature overnight before it was concentrated in vacuo. The crude residue was partitioned between DCM (20 mL) and water (5 mL). The organic solution was washed with saturated aqueous NaHCO3 (2×5 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by MPLC on Silica gel (eluting with 2-4% MeOH/DCM) to afford the title compound. 1H NMR (400 MHz, CD3OD) δ 8.13 (s, 1H), 7.55 (d, J=8.8 Hz, 2H), 7.24 (d, J=9.2 Hz, 2H), 4.35-4.28 (m, 1H), 3.74 (s, 3H), 3.52-3.34 (m, 1H), 2.68-2.62 (m, 1H), 2.55-2.52 (m, 1H), 2.24-2.16 (m, 3H), 2.00-1.90 (m, 1H), 1.73-1.70 (m, 1H). MS ESI: [M+H]+ m/z 401.

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe crude residue was partitioned between DCM (20 mL) and water (5 mL)
  3. washThe organic solution was washed with saturated aqueous NaHCO3 (2×5 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by MPLC on Silica gel (eluting with 2-4% MeOH/DCM)

Sources & evidence

ORD record
ord-00cc78b4c0dd40d99f13151a9c9e3db3
Source dataset
uspto-grants-2015_02
Patent number
US08962608B2

Reaction notes

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