Diisopropylethylamine → HCID 89612474, compound

HRID 1402208Notes

Reaction equation

HRID 1402208 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@@H:3]1[C:7]1[N:11]2[CH:12]=[C:13]([O:16][C@H:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C@@H:20]([NH2:27])[CH2:19][CH2:18]3)[CH:14]=[CH:15][C:10]2=[N:9][N:8]=1.ClC(Cl)(Cl)C[O:31][C:32](=O)[NH:33][C:34]1[N:35]([C:43]2[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][CH:44]=2)[N:36]=[C:37]([C:39]([CH3:42])([CH3:41])[CH3:40])[CH:38]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:39]([C:37]1[CH:38]=[C:34]([NH:33][C:32]([NH:27][C@@H:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@H:17]([O:16][C:13]3[CH:14]=[CH:15][C:10]4[N:11]([C:7]([C@H:3]5[CH2:4][CH2:5][CH2:6][N:2]5[CH3:1])=[N:8][N:9]=4)[CH:12]=3)[CH2:18][CH2:19]2)=[O:31])[N:35]([C:43]2[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][CH:44]=2)[N:36]=1)([CH3:42])([CH3:40])[CH3:41]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 89624081HCID 89624081, compound

Product 1

HCID 89612474HCID 89612474, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 60b (123 mg, 0.339 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; 140 mg, 0.346 mmol) in 1,4-dioxane (4 mL) and DIPEA (91 μL, 0.52 mmol) was stirred at 93° C. for 3.25 h. The cooled mixture was concentrated in vacuo. The residue was purified by FCC, using 0-20% MeOH in DCM, to give the impure product. Further purification by HPLC (C18 X-select column, 25-70% MeCN in H2O, 0.1% formic acid) gave the title compound as a white powder after freeze-drying (118 mg, 56%). LCMS (Method 5): Rt 3.67 min, m/z 619.2 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.80-2.27 (11H, m), 2.31-2.40 (4H, m), 3.11-3.18 (1H, m), 3.98 (1H, t, J 8.2), 4.78-4.86 (1H, m), 5.42 (1H, t, J 4.3), 6.32 (1H, s), 7.09 (1H, d, J 8.5), 7.26-7.42 (9H, m), 7.75 (1H, dd, J 9.7, 1.0), 8.03 (1H, s), 8.28 (1H, d, J 1.0).

Workup

  1. concentrationThe cooled mixture was concentrated in vacuo
  2. customThe residue was purified by FCC
  3. customto give the impure product
  4. customFurther purification by HPLC (C18 X-select column, 25-70% MeCN in H2O, 0.1% formic acid)

Sources & evidence

ORD record
ord-bf4b8a0703804072a26072630da50f24
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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