Diisopropylethylamine → HCID 71603793, compound

HRID 2285159Notes

Reaction equation

HRID 2285159 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([O:12][C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([N:22](/C=C/C)/C=C/C)=[N:20][N:21]=3)[CH:18]=2)[CH2:4][CH2:3]1.ClC(Cl)(Cl)CO[C:33](=[O:51])[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>CN(C=O)C.CO>[NH2:22][C:19]1[N:17]2[CH:18]=[C:13]([O:12][C@H:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:2]([NH:1][C:33]([NH:34][C:35]4[N:36]([C:44]5[CH:45]=[CH:46][C:47]([CH3:50])=[CH:48][CH:49]=5)[N:37]=[C:38]([C:40]([CH3:42])([CH3:41])[CH3:43])[CH:39]=4)=[O:51])[CH2:3][CH2:4]3)[CH:14]=[CH:15][C:16]2=[N:21][N:20]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86687164HCID 86687164, compound

Product 1

HCID 71603793HCID 71603793, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of Intermediate 101c (1.33 g, 3.54 mmol), (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (for reference procedure see Synthetic Communications, 2009, 39, 3999-4009, which is incorporated herein by reference in its entirety; 2.0 g, 4.96 mmol) and DIPEA (1.82, 14.16 mmol) in DMF (20 mL) was stirred at RT for 20 h. The reaction mixture was diluted with MeOH and loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% [2M NH3 in MeOH] in DCM, followed by recrystallization from 5% MeOH in DCM (few drops of cyclohexane added to start recrystallization), to give the title compound (760 mg, 39%) as an off white dust. LCMS (Method 5): Rt 3.81 min, m/z 551 [MH+]. NMR (400 MHz, CD3OD): 1.34 (9H, s), 1.86-2.08 (2H, m), 2.09-2.19 (1H, m), 2.22-2.34 (1H, m), 2.42 (3H, s), 4.89-4.96 (1H, m), 5.32 (1H, t, J=4.4 Hz), 6.37 (1H, s), 7.05 (1H, dd, J=10.0, 2.1 Hz), 7.23-7.44 (9H, m), 7.83 (1H, d, J=2.0 Hz).

Workup

  1. washThe cartridge was washed with MeOH
  2. washthe product eluted with 2M NH3 in MeOH
  3. additionThe product containing fractions
  4. concentrationwere concentrated in vacuo
  5. customthe resultant residue was purified by FCC on silica
  6. customfollowed by recrystallization from 5% MeOH in DCM (few drops of cyclohexane added to start recrystallization)

Sources & evidence

ORD record
ord-ad13a23c5f2941e49e41406d7cc0d52a
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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