Diisopropylethylamine → 1-[5-tert-Butyl-2-(3-hydroxymethyl-4-triisopropylsilanyloxy-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

HRID 60656Notes

Reaction equation

HRID 60656 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:35])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[CH:20][C:19]([O:22][Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])=[C:18]([CH2:33][OH:34])[CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:38][C@H:39]1[CH2:44][CH2:43][CH2:42][CH2:41][N:40]1[C:45]1[N:49]2[CH:50]=[C:51]([O:54][C@H:55]3[C:64]4[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=4)[C@@H:58]([NH2:65])[CH2:57][CH2:56]3)[CH:52]=[CH:53][C:48]2=[N:47][N:46]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:65][C@@H:58]2[C:59]3[C:64](=[CH:63][CH:62]=[CH:61][CH:60]=3)[C@H:55]([O:54][C:51]3[CH:52]=[CH:53][C:48]4[N:49]([C:45]([N:40]5[CH2:41][CH2:42][CH2:43][CH2:44][C@@H:39]5[CH3:38])=[N:46][N:47]=4)[CH:50]=3)[CH2:56][CH2:57]2)=[O:35])[N:8]([C:16]2[CH:21]=[CH:20][C:19]([O:22][Si:23]([CH:30]([CH3:32])[CH3:31])([CH:24]([CH3:26])[CH3:25])[CH:27]([CH3:29])[CH3:28])=[C:18]([CH2:33][OH:34])[CH:17]=2)[N:9]=1)([CH3:14])([CH3:15])[CH3:13]

Participants

5

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 123978986HCID 123978986, compound

Product 1

HCID 1233790051-[5-tert-Butyl-2-(3-hydroxymethyl-4-triisopropylsilanyloxy-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}-ureaYield 58%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 61d (173 mg, 0.29 mmol), Intermediate B (100 mg, 0.27 mmol) and DIPEA (58 μL, 0.33 mmol) in 1,4-dioxane (2.9 mL) was stirred at 70° C. for 42 h. The mixture was evaporated in vacuo and the residue was partitioned between DCM and water. The aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-5% MeOH in DCM, to give the title compound as a cream colored glass (127 mg, 58%). LCMS (Method 3): Rt 4.97 min, m/z 821 [MH+].

Workup

  1. customThe mixture was evaporated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. extractionThe aqueous layer was then extracted with DCM (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-00704676e43142b2b712176cd5217c17
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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