Diisopropylethylamine → 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-triisopropylsilanyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 1402216Notes

Reaction equation

HRID 1402216 reaction equation
[CH:1]([Si:4]([CH:36]([CH3:38])[CH3:37])([CH:33]([CH3:35])[CH3:34])[O:5][C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]2[N:16]3[CH:17]=[C:18]([O:21][C@H:22]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[C@@H:25]([NH2:32])[CH2:24][CH2:23]4)[CH:19]=[CH:20][C:15]3=[N:14][N:13]=2)[CH2:7]1)([CH3:3])[CH3:2].ClC(Cl)(Cl)C[O:42][C:43](=O)[NH:44][C:45]1[N:46]([C:54]2[CH:59]=[CH:58][C:57]([CH3:60])=[CH:56][CH:55]=2)[N:47]=[C:48]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH:49]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:50]([C:48]1[CH:49]=[C:45]([NH:44][C:43]([NH:32][C@@H:25]2[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@H:22]([O:21][C:18]3[CH:19]=[CH:20][C:15]4[N:16]([C:12]([N:8]5[CH2:9][CH2:10][CH2:11][C@H:6]([O:5][Si:4]([CH:1]([CH3:3])[CH3:2])([CH:33]([CH3:35])[CH3:34])[CH:36]([CH3:38])[CH3:37])[CH2:7]5)=[N:13][N:14]=4)[CH:17]=3)[CH2:23][CH2:24]2)=[O:42])[N:46]([C:54]2[CH:59]=[CH:58][C:57]([CH3:60])=[CH:56][CH:55]=2)[N:47]=1)([CH3:53])([CH3:51])[CH3:52]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86687069(1S,4R)-4-[3-((S)-3-Triisopropylsilanyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 866870701-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-triisopropylsilanyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 60%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 63c (140 mg, 0.261 mmol) and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (Synthetic Communications, 2009, 39, 3999-4009, which is incorporated herein by reference in its entirety; 106 mg, 0.261 mmol) in 1,4-dioxane (3 mL) and DIPEA (70 μL, 0.4 mmol) was stirred at 90° C. for 3 h. The cooled mixture was concentrated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give the title compound as a pale brown gum (124 mg, 60%). LCMS (Method 3): Rt 5.43 min, m/z 791 [MH+].

Workup

  1. concentrationThe cooled mixture was concentrated in vacuo
  2. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-c8329c4c7f9542f5bdd96ebb7034509c
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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