Diisopropylethylamine → 1-[5-tert-butyl-2-(3-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 2285257Notes

Reaction equation

HRID 2285257 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[N:11]2[CH:12]=[C:13]([O:16][C@H:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C@@H:20]([NH2:27])[CH2:19][CH2:18]3)[CH:14]=[CH:15][C:10]2=[N:9][N:8]=1.ClC(Cl)(Cl)C[O:31][C:32](=O)[NH:33][C:34]1[N:35]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([CH2:49][OH:50])[CH:44]=2)[N:36]=[C:37]([C:39]([CH3:42])([CH3:41])[CH3:40])[CH:38]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[NH3:2].[C:39]([C:37]1[CH:38]=[C:34]([NH:33][C:32]([NH:27][C@@H:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@H:17]([O:16][C:13]3[CH:14]=[CH:15][C:10]4[N:11]([C:7]([C@@H:3]5[CH2:4][CH2:5][CH2:6][N:2]5[CH3:1])=[N:8][N:9]=4)[CH:12]=3)[CH2:18][CH2:19]2)=[O:31])[N:35]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([CH2:49][OH:50])[CH:44]=2)[N:36]=1)([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 86687007[5-tert-Butyl-2-(3-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl esterHCID 117666105(1S,4R)-4-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 2

HCID 222AmmoniaHCID 866872701-[5-tert-butyl-2-(3-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 85%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of Intermediate 5c (1.60 g, 4.40 mmol) and Intermediate 29c (1.85 g, 4.40 mmol) in dioxane (20 mL) was treated with DIPEA (1.15 mL, 6.60 mmol) and the reaction mixture was heated at 70° C. for 36 h. The mixture was concentrated in vacuo and the residue was dissolved in DCM (150 mL) and washed with water (2×75 mL) and brine (75 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo and the foam obtained purified by FCC, using 0-5% MeOH in DCM then 0-5% [2M NH3 in MeOH] in DCM to afford the title compound as a yellow foamy solid (0.94 g, 85%). LCMS (Method 3): Rt 2.76 min, m/z 635 [MH+].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in DCM (150 mL)
  3. washwashed with water (2×75 mL) and brine (75 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customthe foam obtained
  8. custompurified by FCC

Sources & evidence

ORD record
ord-98f887d4aec14ba1822ef84d5930fac0
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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