Diisopropylethylamine → HCID 58431092, compound

HRID 1040524Notes

Reaction equation

HRID 1040524 reaction equation
[C:1]([C:3]1[CH:35]=[CH:34][C:6]([CH2:7][C@@:8]2([CH3:33])[N:12]3[C:13]([C:16]([NH:18][C@@H:19]([CH3:23])[C:20]([OH:22])=O)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:24]3[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=3)[C:9]2=[O:32])=[CH:5][CH:4]=1)#[N:2].Cl.[NH2:37][C@H:38]([CH3:42])[C:39]([NH2:41])=[S:40].C(N(C(C)C)CC)(C)C.C1C=NC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:39]([C@H:38]([NH:37][C:20]([C@@H:19]([NH:18][C:16]([C:13]1[N:12]2[C@@:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:35][CH:34]=3)([CH3:33])[C:9](=[O:32])[N:10]([C:24]3[CH:25]=[C:26]([Cl:31])[CH:27]=[C:28]([Cl:30])[CH:29]=3)[C:11]2=[N:15][CH:14]=1)=[O:17])[CH3:23])=[O:22])[CH3:42])(=[S:40])[NH2:41]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 55285661HCID 55285661, compoundHCID 58431091HCID 58431091, compound

Product 1

HCID 58431092HCID 58431092, compoundYield 102.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (S)-2-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-propionic acid, (129 mg, 0.25 mmol), (R)-2-amino-thiopropionamide hydrochloride (53 mg, 0.38 mmol) and diisopropylethylamine (0.175 mL, 1.01 mmol) in DMF (1 mL) was stirred at room temperature for 10 min. After cooling to 0° C., HOAt (69 mg, 0.50 mmol) and HATU (105 mg, 0.25 mmol) were added. The clear yellow reaction mixture was allowed to warm to room temperature slowly overnight. The reaction mixture was partitioned between ethyl acetate (35 mL) and 1 M HCl (10 mL). The organic phase was washed with saturated NaHCO3 solution and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (0-10% MeOH in dichloromethane) to afford 154 mg of the title compound as a white foam, m/z 598.4 [M+1]+.

Workup

  1. temperatureto warm to room temperature slowly overnight
  2. customThe reaction mixture was partitioned between ethyl acetate (35 mL) and 1 M HCl (10 mL)
  3. washThe organic phase was washed with saturated NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (0-10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-7e71b7135f9e481099f0074488c29d1d
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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