Diisopropylethylamine → HCID 86687199, compound

HRID 2282662Notes

Reaction equation

HRID 2282662 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[C:8]1[N:12]2[CH:13]=[C:14]([O:17][C@H:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C@@H:21]([NH2:28])[CH2:20][CH2:19]3)[CH:15]=[CH:16][C:11]2=[N:10][N:9]=1.ClC(Cl)(Cl)C[O:32][C:33](=O)[NH:34][C:35]1[N:36]([CH2:44][CH2:45][OH:46])[N:37]=[C:38]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:39]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:40]([C:38]1[CH:39]=[C:35]([NH:34][C:33]([NH:28][C@@H:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@H:18]([O:17][C:14]3[CH:15]=[CH:16][C:11]4[N:12]([C:8]([C@@H:3]5[CH2:4][CH2:5][CH2:6][CH2:7][N:2]5[CH3:1])=[N:9][N:10]=4)[CH:13]=3)[CH2:19][CH2:20]2)=[O:32])[N:36]([CH2:44][CH2:45][OH:46])[N:37]=1)([CH3:43])([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86686717[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl esterHCID 86687198HCID 86687198, compound

Product 1

HCID 86687199HCID 86687199, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of Intermediate 120c (35 mg, 0.10 mmol), Intermediate 110b (54 mg, 0.15 mmol) and DIPEA (53 μL, 4, 0.30 mmol) in dioxane (1 mL) was stirred at 50° C. overnight. After cooling, the reaction mixture was loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The resultant residue was purified by FCC on silica, using a gradient of 1-8% MeOH in DCM followed by MDAP (Method 7) purification, to afford the title compound (4 mg, 7%) as a glassy white solid. LCMS (Method 5): Rt 3.02 min, m/z 586 [MH+]. 1H NMR (400 MHz, d4-MeOD): 1.20-1.30 (2H, m), 1.25 (9H, s), 1.40-1.52 (1H, m), 1.63-1.83 (3H, m), 1.85-1.92 (2H, m), 2.01 (3H, s), 2.06-2.20 (3H, m), 2.24 (1H, td, J=11.7, 3.1 Hz), 2.31-2.38 (1H, m), 3.04-3.09 (1H, m), 3.76-3.81 (1H, m), 3.81 (2H, t, J=5.4 Hz), 4.08 (2H, t, J=5.4 Hz), 4.98 (1H, dd, J=8.1, 6.5 Hz), 5.36 (1H, t, J=3.8 Hz), 6.12 (1H, s), 7.24 (1H, t, J=7.4 Hz), 7.28-7.37 (3H, m), 7.44 (1H, d, J=7.8 Hz), 7.66 (1H, dd, J=9.9, 0.6 Hz), 8.46 (1H, d, J=1.9 Hz).

Workup

  1. temperatureAfter cooling
  2. washThe cartridge was washed with MeOH
  3. washthe product eluted with 2M NH3 in MeOH
  4. customThe resultant residue was purified by FCC on silica
  5. customfollowed by MDAP (Method 7) purification

Sources & evidence

ORD record
ord-689d39c24d97466a8923c7b279c4a649
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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