Diisopropylethylamine → HCID 86687192, compound

HRID 2285185Notes

Reaction equation

HRID 2285185 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:19])[NH:6][C:7]1[N:8]([CH2:16][CH2:17][OH:18])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:22][C@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]1[C:29]1[N:33]2[CH:34]=[C:35]([O:38][C@H:39]3[C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[C@@H:42]([NH2:49])[CH2:41][CH2:40]3)[CH:36]=[CH:37][C:32]2=[N:31][N:30]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:49][C@@H:42]2[C:43]3[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=3)[C@H:39]([O:38][C:35]3[CH:36]=[CH:37][C:32]4[N:33]([C:29]([N:24]5[CH2:25][CH2:26][CH2:27][CH2:28][C@@H:23]5[CH3:22])=[N:30][N:31]=4)[CH:34]=3)[CH2:40][CH2:41]2)=[O:19])[N:8]([CH2:16][CH2:17][OH:18])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

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 86687106(1S,4R)-4-[3-((S)-2-Methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 86687192HCID 86687192, compoundYield 15.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of Intermediate 110b (143 mg, 0.40 mmol), Intermediate 81d (1151 mg, 0.40 mmol) and DIPEA (82 μL, 0.50 mmol) in dioxane (5 mL) was stirred at 100° C. for 4 h. After cooling, the reaction mixture was concentrated in vacuo and then partitioned between water and DCM. The aqueous phase was extracted with DCM (×3) and the combined organic layers were washed with brine, dried through a phase separator and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 3-15% MeOH in DCM followed by MDAP (Method 7) purification, to afford the title compound (36 mg, 15%) as a glassy white solid. LCMS (Method 5): Rt 4.02 min, m/z 587 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.92 (3H, d, J=6.3 Hz), 1.21 (9H, s), 1.44-1.57 (2H, m), 1.60-1.74 (2H, m), 1.74-1.87 (2H, m), 1.88-2.22 (4H, m), 2.86-2.96 (1H, m), 3.12-3.20 (2H, m), 3.63-3.71 (2H, m), 3.95 (2H, t, J=6.0 Hz), 4.82-4.91 (1H, m), 5.00 (1H, br s), 5.54 (1H, t, J=4.3 Hz), 6.07 (1H, s), 7.10 (1H, d, J=8.6 Hz), 7.22 (1H, dd, J=9.8, 2.2 Hz), 7.26-7.32 (1H, m), 7.35-7.42 (3H, m), 7.65 (1H, d, J=10.8 Hz), 7.71 (1H, d, J=2.1 Hz), 8.19-8.23 (1H, m).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. custompartitioned between water and DCM
  4. extractionThe aqueous phase was extracted with DCM (×3)
  5. washthe combined organic layers were washed with brine
  6. customdried through a phase separator
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by FCC on silica
  9. customfollowed by MDAP (Method 7) purification

Sources & evidence

ORD record
ord-aaa7bc16b90847a6ad536d02d1b72fed
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

Loading…