Diisopropylethylamine → HCID 89612603, compound

HRID 1402223Notes

Reaction equation

HRID 1402223 reaction equation
[N:1]1([C:8]2[N:12]3[CH:13]=[C:14]([O:17][C@H:18]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[C@@H:21]([NH2:28])[CH2:20][CH2:19]4)[CH:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.ClC(Cl)(Cl)C[O:32][C:33](=O)[NH:34][C:35]1[N:36]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[N:37]=[C:38]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:39]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[N:1]1([C:8]2[N:12]3[CH:13]=[C:14]([O:17][C@H:18]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[C@@H:21]([NH:28][C:33]([NH:34][C:35]5[N:36]([C:44]6[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=6)[N:37]=[C:38]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:39]=5)=[O:32])[CH2:20][CH2:19]4)[CH:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86687076HCID 86687076, compound

Product 1

HCID 89612603HCID 89612603, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 67b (173 mg, 0.458 mmol) and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (Synthetic Communications, 2009, 39, 3999-4009, which is incorporated herein by reference in its entirety; 186 mg, 0.458 mmol) in 1,4-dioxane (3 mL) and DIPEA (122 μL, 0.700 mmol) was stirred at 95° C. for 3.5 h. The cooled mixture was concentrated in vacuo. The residue was purified by FCC, using 0-14% [2M NH3 in MeOH] in DCM. Further purification by FCC, using 0-10% MeOH in DCM, gave impure product. This was further purified by HPLC (C18 X-select column, 30-98% MeCN in H2O, 0.1% HCO2H) to give impure product. Further purified by HPLC (XBridge column, 35-98% MeCN in H2O, 0.1% NH4OH) to give an off-white powder after freeze-drying (50 mg). This material was further purified by MDAP (Method 7) to give the title compound as a white solid (28 mg, 10%). LCMS (Method 5): Rt 4.77 min, m/z 633.2 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.64-1.71 (4H, m), 1.74-1.97 (6H, m), 1.99-2.18 (2H, m), 2.36 (3H, s), 3.38-3.43 (4H, m, under water signal), 4.77-4.85 (1H, m), 5.47 (1H, t, J 4.3), 6.32 (1H, s), 7.07-7.14 (2H, m), 7.25-7.40 (8H, m), 7.55-7.59 (2H, m), 8.06 (1H, s).

Workup

  1. concentrationThe cooled mixture was concentrated in vacuo
  2. customThe residue was purified by FCC
  3. customFurther purification by FCC
  4. customgave impure product
  5. customThis was further purified by HPLC (C18 X-select column, 30-98% MeCN in H2O, 0.1% HCO2H)
  6. customto give impure product
  7. customFurther purified by HPLC (XBridge column, 35-98% MeCN in H2O, 0.1% NH4OH)
  8. customto give an off-white powder
  9. customafter freeze-drying (50 mg)
  10. customThis material was further purified by MDAP (Method 7)

Sources & evidence

ORD record
ord-65056d224874404892f38f111c755ca1
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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