Tetrabutylammonium Fluoride → 1-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-hydroxymethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 2200039Notes

Reaction equation

HRID 2200039 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([C:23]1[CH:24]=[C:25]([NH:29][C:30]([NH:32][C@@H:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C@H:36]([O:43][C:44]3[CH:45]=[CH:46][C:47]4[N:48]([C:50]([N:53]5[CH2:58][CH2:57][CH:56]([CH2:59][O:60][Si](C(C)C)(C(C)C)C(C)C)[CH2:55][CH2:54]5)=[N:51][N:52]=4)[CH:49]=3)[CH2:35][CH2:34]2)=[O:31])[N:26]([CH3:28])[N:27]=1)([CH3:22])([CH3:21])[CH3:20]>C1COCC1.C(Cl)Cl>[C:19]([C:23]1[CH:24]=[C:25]([NH:29][C:30]([NH:32][C@@H:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C@H:36]([O:43][C:44]3[CH:45]=[CH:46][C:47]4[N:48]([C:50]([N:53]5[CH2:58][CH2:57][CH:56]([CH2:59][OH:60])[CH2:55][CH2:54]5)=[N:51][N:52]=4)[CH:49]=3)[CH2:35][CH2:34]2)=[O:31])[N:26]([CH3:28])[N:27]=1)([CH3:22])([CH3:20])[CH3:21]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 123647418HCID 123647418, compound

Product 1

HCID 1177290431-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-hydroxymethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 60.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M solution in THF, 211 μL, 0.211 mmol) was added to a solution of Intermediate 14f (110 mg, 0.151 mmol) in THF (3 mL) and the reaction mixture was stirred at RT for 1 h. The mixture was diluted with DCM (5 mL) and washed with water (2×5 mL) and brine (5 mL). The organic layer was 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 (52 mg, 60%). LCMS (Method 3): Rt: 2.91 min, m/z 573 [MH+].

Workup

  1. washwashed with water (2×5 mL) and brine (5 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-c9827be2e38b4a13a949f611ab5deafc
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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