Diethyl Ether → HCID 86687273, compound

HRID 630961Notes

Reaction equation

HRID 630961 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:60])[NH:37][C:38]2[N:39]([C:47]3[CH:52]=[CH:51][CH:50]=[C:49]([N:53]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[CH3:54])[CH: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.CCOCC>O1CCOCC1>[CH:36]([OH:60])=[O:35].[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][CH:50]=[C:49]([N:53]([CH2:55][CH2:56][N:57]([CH3:58])[CH3:59])[CH3:54])[CH:48]=2)[N:40]=1)([CH3:46])([CH3:44])[CH3:45]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 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 86687275HCID 86687275, compound

Product 1

HCID 86687273HCID 86687273, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of Intermediate 81d (26 mg, 0.07 mmol) in 1,4-dioxane (2 mL) was treated with Intermediate 150c (30 mg, 0.07 mmol) and DIPEA (24 μL, 0.13 mmol) and the mixture was stirred at 70° C. for 18 h. After cooling to RT the mixture was concentrated in vacuo. The residue was purified by FCC, using 0-20% MeOH in DCM, then by prep HPLC (C18 column, 10-98% MeCN in H2O, 0.1% HCO2H) over 20 mins. Concentration of the fractions in vacuo gave pale yellow glass. Trituration with Et2O gave the title compound as an off white solid (20 mg, 40%). LCMS (Method 5): Rt 3.70 min, m/z 719.6 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.4 Hz), 1.27 (9H, s), 1.47-1.53 (2H, m), 1.64-1.71 (2H, m), 1.77-1.97 (4H, m), 2.00-2.15 (2H, m), 2.16 (3H, s), 2.39 (2H, t, J=7.2 Hz), 2.87-2.92 (1H, m), 2.93 (3H, s), 3.13-3.21 (4H, m), 3.35-3.46 (4H, m), 4.80-4.87 (1H, m), 5.52 (1H, t, J=4.3 Hz), 6.32 (1H, s), 6.68-6.72 (3H, m), 7.13 (1H, d, J=8.6 Hz), 7.19 (1H, dd, J=9.7, 2.2 Hz), 7.24-7.38 (5H, m), 7.64 (1H, d, J=9.7 Hz), 7.69 (1H, m), 8.11 (1H, s).

Workup

  1. temperatureAfter cooling to RT the mixture
  2. concentrationwas concentrated in vacuo
  3. customThe residue was purified by FCC
  4. waitby prep HPLC (C18 column, 10-98% MeCN in H2O, 0.1% HCO2H) over 20 mins
  5. customConcentration of the fractions in vacuo gave pale yellow glass

Sources & evidence

ORD record
ord-81f7f12c26bf4461bbd2df9c3a45c739
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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