Diisopropylethylamine → HCID 57919167, compound

HRID 2381409Notes

Reaction equation

HRID 2381409 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:13]=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.[NH2:54][C:55]1[CH:59]=[CH:58][N:57]([CH2:60][C:61]([CH3:64])([OH:63])[CH3:62])[N:56]=1>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:13]=[N:12]2)[C:8]([NH:54][C:55]2[CH:59]=[CH:58][N:57]([CH2:60][C:61]([OH:63])([CH3:62])[CH3:64])[N:56]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 46223054HCID 46223054, compound2×HCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol2×

Product 1

HCID 57919167HCID 57919167, compoundYield 16.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(6-oxo-4-phenoxy-6H-pyridazin-1-yl)-propionic acid (Intermediate 19, 100.6 mg, 0.30 mmol) in methylene chloride (1.70 mL, 0.18M) at 25° C. was treated with N,N-diisopropylethylamine (160 μL, 0.91 mmol) followed by N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (110.6 mg, 0.36 mmol). The resulting solution was stirred at 25° C. for 2.5 h. After this time, the reaction was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1, 61.8 mg, 0.39 mmol). The resulting solution was stirred at 25° C. for 2 d. After this time, the reaction was partitioned between water (75 mL) and methylene chloride (3×75 mL). The combined organics were washed with water (3×100 mL), dried over sodium sulfate and concentrated in vacuo. Silica gel column chromatography (ISCO 40 g, 1/1-3/1 ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(6-oxo-4-phenoxy-6H-pyridazin-1-yl)-propionamide (23.6 mg, 16.5%) as a white solid; ES+-HRMS m/e calcd for C25H31N5O4 [M+H+] 466.2449, found 466.2450. 1H-NMR (300 MHz, DMSO-d6) δ ppm 1.05 (s, 3H), 1.06 (s, 3H), 1.00-1.76 (m, 9H), 1.91 (m, 1H), 2.28 (m, 1H), 3.89 (s, 2H), 4.67 (s, 1H), 5.46 (dd, J=3.9, J=11.2 Hz, 1H), 5.72 (d, J=2.7 Hz, 1H), 6.39 (d, J=2.1 Hz, 1H), 7.29 (d, J=7.5 Hz, 2H), 7.36 (t, J=7.5 Hz, 1H), 7.46-7.64 (m, 3H), 8.12 (d, J=2.7 Hz, 1H), 10.79 (s, 1H).

Workup

  1. stirringThe resulting solution was stirred at 25° C. for 2 d
  2. customAfter this time, the reaction was partitioned between water (75 mL) and methylene chloride (3×75 mL)
  3. washThe combined organics were washed with water (3×100 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8b1204d311e74352b99d4f44e65f805b
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

Loading…