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

HRID 60685Notes

Reaction equation

HRID 60685 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:33])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH2:24][CH2:25][O:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][O:28]3)[CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:36][C@H:37]1[CH2:41][CH2:40][CH2:39][N:38]1[C:42]1[N:46]2[CH:47]=[C:48]([O:51][C@H:52]3[C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[C@@H:55]([NH2:62])[CH2:54][CH2:53]3)[CH:49]=[CH:50][C:45]2=[N:44][N:43]=1.CCN(C(C)C)C(C)C>O1CCOCC1.C(Cl)Cl>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:62][C@@H:55]2[C:56]3[C:61](=[CH:60][CH:59]=[CH:58][CH:57]=3)[C@H:52]([O:51][C:48]3[CH:49]=[CH:50][C:45]4[N:46]([C:42]([N:38]5[CH2:39][CH2:40][CH2:41][C@@H:37]5[CH3:36])=[N:43][N:44]=4)[CH:47]=3)[CH2:53][CH2:54]2)=[O:33])[N:8]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH2:24][CH2:25][O:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][O:28]3)[CH:17]=2)[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 117729600(1S,4R)-4-[3-((S)-2-Methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineHCID 117729763(5-tert-Butyl-2-{4-chloro-3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 1177298451-(5-tert-Butyl-2-{4-chloro-3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 19.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 53b (238 mg, 0.41 mmol), Intermediate 78b (220 mg, 0.61 mmol) and DIPEA (158 μL, 0.91 mmol) in dioxane (2.5 mL) was heated at 60° C. for 18 h. The reaction mixture was cooled and diluted with DCM (5 mL). The organic layer was washed with water (2×5 mL), passed through a phase separator and concentrated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to afford the title compound (62 mg, 19%). LCMS (Method 3): Rt: 4.00 min, m/z 783/785 [MH+].

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe organic layer was washed with water (2×5 mL)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-cfe6ff9f4bfd40dca5ae323ccb53eba9
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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