Diisopropylethylamine → 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(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-yl}-urea dichloromethane

HRID 2285303Notes

Reaction equation

HRID 2285303 reaction equation
[Cl:1][C:2](Cl)([Cl:25])CO[C:5](=[O:24])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:27][C@H:28]1[CH2:33][CH2:32][CH2:31][CH2:30][N:29]1[C:34]1[N:38]2[CH:39]=[C:40]([O:43][C@H:44]3[C:53]4[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=4)[C@@H:47]([NH2:54])[CH2:46][CH2:45]3)[CH:41]=[CH:42][C:37]2=[N:36][N:35]=1.CCN(C(C)C)C(C)C>O1CCOCC1.C(Cl)Cl>[Cl:1][CH2:2][Cl:25].[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:54][C@@H:47]2[C:48]3[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=3)[C@H:44]([O:43][C:40]3[CH:41]=[CH:42][C:37]4[N:38]([C:34]([N:29]5[CH2:30][CH2:31][CH2:32][CH2:33][C@@H:28]5[CH3:27])=[N:35][N:36]=4)[CH:39]=3)[CH2:45][CH2:46]2)=[O:24])[N:8]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][CH:17]=2)[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

6

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 89612285[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 866873151-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(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-yl}-urea dichloromethaneYield 87%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A red-brown solution of Intermediate 33a (883 mg, 2.10 mmol), Intermediate 81d (755 mg, 2.00 mmol) and DIPEA (0.44 mL, 2.5 mmol) in dry dioxane (20 mL) was stirred at 70° C. for 16 h, and at 80° C. for 5 h. The cooled solution was concentrated in vacuo, suspended in water (15 mL) and extracted with DCM (2×15 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave a brown oil. Flash chromatography (silica 80 g, 4-8% MeOH in DCM) gave the title compound as a pale yellow foam (1.27 g, 87%). LCMS (Method 3): Rt 3.61 min, m/z 649 [MH+].

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. extractionextracted with DCM (2×15 mL)
  3. concentrationconcentrated in vacuo
  4. customto leave a brown oil

Sources & evidence

ORD record
ord-420d8aeb434f47d8afeba11dad78cfaf
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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