Diisopropylethylamine → HCID 86687245, compound

HRID 1402402Notes

Reaction equation

HRID 1402402 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N: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.C1([O:35][C:36](=O)[NH:37][C:38]2[N:39]([C:47]3[CH:52]=[CH:51][N:50]=[C:49]([N:53]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[CH3:54])[N:48]=3)[N:40]=[C:41]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:42]=2)C=CC=CC=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:43]([C:41]1[CH:42]=[C:38]([NH:37][C:36]([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]([N:3]5[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]5[CH3:1])=[N:9][N:10]=4)[CH:13]=3)[CH2:19][CH2:20]2)=[O:35])[N:39]([C:47]2[CH:52]=[CH:51][N:50]=[C:49]([N:53]([CH2:55][CH2:56][N:57]([CH3:58])[CH3:59])[CH3:54])[N:48]=2)[N:40]=1)([CH3:46])([CH3:44])[CH3:45]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 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-ylamineHCID 86687244HCID 86687244, compound

Product 1

HCID 86687245HCID 86687245, compoundYield 56.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of Intermediate 81d (25 mg, 0.066 mmol) in 1,4-dioxane (0.7 mL) was treated with Intermediate 140c (32 mg, 0.073 mmol) and DIPEA (0.014 mL, 0.083 mmol) and the mixture was stirred at 70° C. for 18 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown gum. FCC, using 0-8% MeOH in DCM, gave a colourless glass (27 mg). The glass was purified further by HPLC (Phenomenex Gemini C18 column, 5-95% MeCN in H2O, 0.1% HCO2H) over 30 mins. Concentration of the fractions in vacuo gave a colourless glass that was dissolved in ether. A solid was precipitated out of solution by addition of cyclohexane. The solid was filtered off to give the title compound as a white solid (8 mg, 17%). LCMS (Method 5): Rt 4.07 min, m/z 721.6 [MH+]. 1H NMR (400 MHz, d6-DMSO, 353K): 0.92 (3H, d, J=6.4 Hz), 1.29 (9H, s), 1.49-1.58 (2H, m), 1.65-1.72 (2H, m), 1.77-1.86 (2H, m), 1.99 (6H, s), 2.00-2.14 (4H, m), 2.20-2.29 (1H, m), 3.12-3.19 (5H, m), 3.30-3.39 (1H, m), 3.58-3.72 (2H, m), 4.94-5.02 (1H, m), 5.42 (1H, t, J=3.9 Hz), 6.55 (1H, s), 7.03 (1H, d, J=5.5 Hz), 7.15 (1H, dd, J=9.8, 2.3 Hz), 7.22-7.27 (1H, m), 7.31-7.37 (2H, m), 7.41-7.45 (1H, m), 7.56-7.61 (2H, m), 7.70 (1H, br s), 8.35 (1H, d, J=5.5 Hz), 10.18 (1H, br s).

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with DCM (×2)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo to a brown gum

Sources & evidence

ORD record
ord-5711675be96a4ebc8bcc09db436c8724
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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