Diisopropylethylamine → 1-{(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea

HRID 2285254Notes

Reaction equation

HRID 2285254 reaction equation
[CH2:1]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH2:29])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:2]1.ClC(Cl)(Cl)C[O:33][C:34](=O)[NH:35][C:36]1[N:37]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([O:51][CH2:52][CH2:53][OH:54])[CH:46]=2)[N:38]=[C:39]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:40]=1.CCN(C(C)C)C(C)C>O1CCOCC1.C(Cl)Cl>[CH2:2]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:34]([NH:35][C:36]5[N:37]([C:45]6[CH:50]=[CH:49][CH:48]=[C:47]([O:51][CH2:52][CH2:53][OH:54])[CH:46]=6)[N:38]=[C:39]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:40]=5)=[O:33])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:1]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 59151941{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl esterHCID 86687266(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 866872671-{(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-ureaYield 89.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

An orange-brown solution of Intermediate 148d (87.2 mg, 0.224 mmol), Intermediate 148e (100 mg, 0.224 mmol) and DIPEA (0.049 mL, 0.28 mmol) in dry dioxane (3 mL) was stirred at 75° C. for 16 h. The cooled solution was concentrated in vacuo, suspended in water (5 mL) and extracted with DCM (2×5 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave a brown gum. Flash chromatography (silica 12 g, 4-8% MeOH in DCM) gave the title compound as a pale yellow solid (138 mg, 89%). LCMS (Method 3): Rt 3.57 min, m/z 691 [MH+].

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. extractionextracted with DCM (2×5 mL)
  3. concentrationconcentrated in vacuo
  4. customto leave a brown gum

Sources & evidence

ORD record
ord-31543ce1c26649d2bb92dcbb6ddd8496
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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