Diisopropylethylamine → HCID 71598648, compound

HRID 75600Notes

Reaction equation

HRID 75600 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C@H:6]([O:13][C:14]3[CH:15]=[CH:16][C:17]4[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=4)[CH:19]=3)[CH2:7][CH2:8][C@@H:9]2[NH2:12])=[CH:4][CH:3]=1.ClC(Cl)(Cl)C[O:29][C:30](=O)[NH:31][C:32]1[N:33]([CH3:41])[N:34]=[C:35]([C:37]([CH3:40])([CH3:39])[CH3:38])[CH:36]=1.CCN(C(C)C)C(C)C>O1CCOCC1.CCN(C(C)C)C(C)C>[C:37]([C:35]1[CH:36]=[C:32]([NH:31][C:30]([NH:12][C@@H:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[C@H:6]([O:13][C:14]3[CH:15]=[CH:16][C:17]4[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=4)[CH:19]=3)[CH2:7][CH2:8]2)=[O:29])[N:33]([CH3:41])[N:34]=1)([CH3:40])([CH3:38])[CH3:39]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 594208722,2,2-Trichloroethyl (3-tert-butyl-1-methyl-1H-pyrazol-5-yl)carbamate2×HCID 86686698HCID 86686698, compound

Product 1

HCID 71598648HCID 71598648, compoundYield 63.1%

Reagents, catalysts & solvents 2

HCID 81531DiisopropylethylamineCatalystHCID 312751,4-DioxaneSolvent

Procedure

Intermediate 19b (85.0 mg, 0.250 mmol) and (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (US2004/192653, 99 mg, 0.300 mmol) were dissolved in 1,4-dioxane (3 mL) and DIPEA (70 μL, 0.400 mmol). The reaction was heated at reflux for 1.75 h, then more (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (35 mg, 0.100 mmol) and DIPEA (3 drops) were added. After a further 4 h the mixture was concentrated in vacuo. The residue was purified by FCC, using 0-15% MeOH in DCM, to give impure product (82 mg). Further purification twice by HPLC (C18 X-select column, 40-98% MeCN in H2O, 0.1% HCO2H) gave the title compound as a white powder after freeze-drying (44 mg, 34%). LCMS (Method 5): Rt 3.83 min, m/z 520.1 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.21 (9H, s), 1.35-1.43 (6H, m), 1.85-2.25 (4H, m), 3.51-3.62 (4H, m), 4.80-4.91 (1H, m), 5.50-5.57 (1H, m), 6.02 (1H, s), 7.09 (1H, d, J 8.8), 7.11-7.17 (2H, m), 7.20 (1H, dd, J 9.6, 2.2), 7.44-7.50 (1H, m), 7.69 (1H, d, J 9.6), 8.22 (1H, br d), 8.40 (1H, s).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 1.75 h
  3. concentrationAfter a further 4 h the mixture was concentrated in vacuo
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-780d346bcd9742958d34251f7154b85d
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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