1-Hydroxybenzotriazole → HCID 66894751, compound

HRID 19196Notes

Reaction equation

HRID 19196 reaction equation
OC(C)(C)C[N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])=[CH:18][C:17]2=[O:29])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[C:55]([O:59][C:60]([N:62]1[C@H:66]([CH2:67]N2C=CC(N)=N2)[CH2:65][O:64][C:63]1([CH3:75])[CH3:74])=[O:61])([CH3:58])([CH3:57])[CH3:56]>ClCCl>[C:55]([O:59][C:60]([N:62]1[C@H:66]([CH2:67][N:4]2[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[C@@H:11]([N:16]3[CH2:20][C:19]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[Cl:28])=[CH:18][C:17]3=[O:29])[CH2:12][CH:13]([CH3:14])[CH3:15])=[N:5]2)[CH2:65][O:64][C:63]1([CH3:74])[CH3:75])=[O:61])([CH3:58])([CH3:56])[CH3:57]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44240794(S)-2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amideHCID 57920061(R)-4-(3-amino-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester

Product 1

HCID 66894751HCID 66894751, compoundYield 105.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 64, 0.98 g, 3.01 mmol) in dichloromethane (15 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride salt (0.64 g, 3.32 mmol), 1-hydroxybenzotriazole (0.45 g, 3.32 mmol) and (R)-4-(3-amino-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (1.07 g, 1.57 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen and then diluted with dichloromethane, washed with a saturated ammonium chloride solution, water, a saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 100% ethyl acetate/hexanes) to afford (R)-4-(3-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidin-3-carboxylic acid t-butyl ester (1.00 g, 55%) as a white powder: LR-ES-MS m/z calculated for C30H40ClN5O6 [M]+ 601, observed 602 [M+H]+.

Workup

  1. washwashed with a saturated ammonium chloride solution, water
  2. dry with materiala saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate
  3. customThe crude product obtained
  4. concentrationafter concentration
  5. customwas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bc78bf0dc6c74185b48bb03ef7ebd635
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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