Diisopropylethylamine → 1-(5-tert-Butyl-2-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(cis-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 2285146Notes

Reaction equation

HRID 2285146 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([CH3:8])[N:3]1[C:9]1[N:13]2[CH:14]=[C:15]([O:18][C@H:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C@@H:22]([NH2:29])[CH2:21][CH2:20]3)[CH:16]=[CH:17][C:12]2=[N:11][N:10]=1.CCN(C(C)C)C(C)C.ClC(Cl)(Cl)C[O:42][C:43](=O)[NH:44][C:45]1[N:46]([C:54]2[CH:59]=[CH:58][CH:57]=[C:56]([O:60][CH2:61][CH2:62][O:63][CH:64]3[CH2:69][CH2:68][CH2:67][CH2:66][O:65]3)[CH:55]=2)[N:47]=[C:48]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH:49]=1>O1CCOCC1>[C:50]([C:48]1[CH:49]=[C:45]([NH:44][C:43]([NH:29][C@@H:22]2[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C@H:19]([O:18][C:15]3[CH:16]=[CH:17][C:12]4[N:13]([C:9]([N:3]5[C@H:2]([CH3:1])[CH2:7][CH2:6][CH2:5][C@@H:4]5[CH3:8])=[N:10][N:11]=4)[CH:14]=3)[CH2:20][CH2:21]2)=[O:42])[N:46]([C:54]2[CH:59]=[CH:58][CH:57]=[C:56]([O:60][CH2:61][CH2:62][O:63][CH:64]3[CH2:69][CH2:68][CH2:67][CH2:66][O:65]3)[CH:55]=2)[N:47]=1)([CH3:53])([CH3:51])[CH3:52]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86686679(5-tert-Butyl-2-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl esterHCID 89624184(1S,4R)-4-[3-(cis-2,6-Dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 716037911-(5-tert-Butyl-2-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(cis-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of Intermediate 96c (100 mg, 0.25 mmol) in 1,4-dioxane (3.00 mL) was added DIPEA (89.0 μL, 0.51 mmol) and Intermediate 39b (133 mg, 0.25 mmol). The reaction was heated to 70° C. overnight then cooled and partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC using 0-8% MeOH in DCM to give the title compound. LCMS (Method 4): Rt 4.09 min, m/z 777 [MH+].

Workup

  1. temperaturethen cooled
  2. custompartitioned between EtOAc and water
  3. extractionThe aqueous layer was then extracted with EtOAc (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-95033a30d4b548cf8c6e35c9c41bc908
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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