1-Methylimidazole → HCID 57877635, compound

HRID 2266749Notes

Reaction equation

HRID 2266749 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:10]2[CH:14]=[C:13]([C:15]([N:17]3[CH2:22][CH2:21][N:20](C(OCC4C=CC=CC=4)=O)[CH2:19][C@@H:18]3[C:33]([O:35]C)=O)=[O:16])[N:12]=[C:11]2[C:37]2[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=2)[CH:7]=[CH:8][CH:9]=1)[CH3:2].CC([CH:47]1NC(=O)C(CCSC)NC(=O)C(NC(C(NC(C(NC(C(NC(C(N)CC(O)=O)=O)C(O)C)=O)CCSC)=O)CCCNC(N)=N)=O)CSSCC(C(NC(C(NC(C(NC(C(O)=O)C(C)C)=O)CCC(O)=O)=O)CC2C3C(=CC=CC=3)NC=2)=O)NC(=O)C2N(CCC2)C(=O)C(CCCNC(N)=N)NC(=O)C(CC2C=CC(O)=CC=2)NC(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CN[C:48]1=[O:49])C.CN1C=CN=C1.CS(Cl)(=O)=O.C[C@@]1(C([O-])=O)NCCN(C(OCC2C=CC=CC=2)=O)C1>ClCCl>[C:48]([O:35][CH2:33][C@H:18]1[CH2:19][NH:20][CH2:21][CH2:22][N:17]1[C:15]([C:13]1[N:12]=[C:11]([C:37]2[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=2)[N:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)[CH:14]=1)=[O:16])(=[O:49])[CH3:47]

Participants

7

Reactant 5

HCID 13901-MethylimidazoleHCID 31297Methanesulfonyl chlorideHCID 16167454Melanin-concentrating hormoneHCID 86761244HCID 86761244, compoundHCID 86761245HCID 86761245, compound

Product 1

HCID 57877635HCID 57877635, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Benzyl 3-methyl (3R)-4-{[1-(3-ethoxyphenyl)-2-(4-methylphenyl)-1H-imidazol-4-yl]carbonyl}piperazine-1,3-dicarboxylate To a solution of 3.18 g (9.88 mmol) of Intermediate 1 in 75 mL of anhydrous dichloromethane at 0° C. was added 1.5 mL (19 mmol) of 1-methylimidazole followed by 0.80 mL (9.9 mmol) of methanesulfonyl chloride. The resulting mixture was stirred with gradual warming to ambient temperature over 20 min, then re-cooled to 0° C. A solution of 2.39 g (8.59 mmol) of 1-benzyl 3-methyl-(3R)-piperazine-1,3-dicarboxylate in 25 mL of anhydrous dichloromethane was then added and the reaction mixture was allowed to warm to ambient temperature over 1 h. The reaction was then quenched with a saturated aqueous ammonium chloride solution (25 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organic layers were washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified on a Biotage® purification apparatus (silica gel, 40 to 50% ethyl acetate in hexanes gradient) to yield the title compound as a colorless solid. LC/MS 583.5 (M+1).

Workup

  1. temperaturere-cooled to 0° C
  2. temperatureto warm to ambient temperature over 1 h
  3. customThe reaction was then quenched with a saturated aqueous ammonium chloride solution (25 mL)
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  6. washthe combined organic layers were washed with brine (50 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified on a Biotage® purification apparatus (silica gel, 40 to 50% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-56afdc8b46b84be8924b54708caa3a11
Source dataset
uspto-grants-2010_12
Patent number
US07858629B2

Reaction notes

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