1-Hydroxybenzotriazole → HCID 54765736, compound

HRID 1925930Notes

Reaction equation

HRID 1925930 reaction equation
[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:15][C:14]3[CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=4[O:23][C:13]=3[C:12]2=[O:24])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:47][C:48]1[CH:52]=[CH:51][N:50]([CH2:53][C:54]([CH3:57])([OH:56])[CH3:55])[N:49]=1>C(Cl)Cl>[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:15][C:14]3[CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=4[O:23][C:13]=3[C:12]2=[O:24])[C:8]([NH:47][C:48]2[CH:52]=[CH:51][N:50]([CH2:53][C:54]([OH:56])([CH3:55])[CH3:57])[N:49]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 67520924HCID 67520924, compound

Product 1

HCID 54765736HCID 54765736, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of (S)-3-Cyclopentyl-2-(3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionic acid (200 mg, 0.61 mmol) in methylene chloride (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI-HCl) (130 mg, 0.67 mmol), 1-hydroxybenzotriazole (HOBT) (90 mg, 0.67 mmol) and commercially available 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (114 mg, 0.73 mmol). The reaction mixture was stirred for 18 hours at 25° C., under N2. The reaction mixture was diluted with methylene chloride, washed with 2N HCl, saturated sodium bicarbonate solution, and 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 12 g; (0% to 100% ethyl acetate/hexane) to afford (S)-3-Cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide as a white powder, 205 mg (72% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (br. s., 3 H), 1.06 (br. s., 3 H), 1.09-1.83 (m, 10 H), 1.83-1.97 (m, 1 H), 3.75 (s, 2 H), 3.89 (s, 2 H), 4.03 (d, J=19.2 Hz, 1 H), 4.40 (d, J=19.2 Hz, 1 H), 4.67 (s, 1 H), 4.87 (dd, J=10.3, 4.8 Hz, 1 H), 6.44 (d, J=1.8 Hz, 1 H), 7.03-7.15 (m, 2 H), 7.20-7.28 (m, 2 H), 7.53 (d, J=1.8 Hz, 1 H), 10.86 (s, 1 H).

Workup

  1. washwashed with 2N HCl, saturated sodium bicarbonate solution
  2. dry with materiala 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 12 g

Sources & evidence

ORD record
ord-9395d931907b429793fcd4a95b8263f8
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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