Tetrabutylammonium Fluoride → 1-[5-tert-Butyl-2-(4-chloro-3-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-[1,4]oxazepan-4-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 711185Notes

Reaction equation

HRID 711185 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:28][C:29]([NH:31][C@@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C@H:35]([O:42][C:43]3[CH:44]=[CH:45][C:46]4[N:47]([C:49]([N:52]5[CH2:58][CH2:57][CH2:56][O:55][CH2:54][CH2:53]5)=[N:50][N:51]=4)[CH:48]=3)[CH2:34][CH2:33]2)=[O:30])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][Si](C(C)C)(C(C)C)C(C)C)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[C:1]([C:5]1[CH:6]=[C:7]([NH:28][C:29]([NH:31][C@@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C@H:35]([O:42][C:43]3[CH:44]=[CH:45][C:46]4[N:47]([C:49]([N:52]5[CH2:58][CH2:57][CH2:56][O:55][CH2:54][CH2:53]5)=[N:50][N:51]=4)[CH:48]=3)[CH2:34][CH2:33]2)=[O:30])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([OH:17])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 123457706HCID 123457706, compound

Product 1

HCID 863451661-[5-tert-Butyl-2-(4-chloro-3-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-[1,4]oxazepan-4-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureaYield 29.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 64a (243 mg, 0.29 mmol) and TBAF (1M in THF, 1.3 mL, 1.33 mmol) in THF (3 mL) was stirred at RT for 1 h, then diluted with water and extracted with DCM (3×20 mL). The combined organics were dried and concentrated in vacuo. The residue was purified by FCC, using 0-5% [2M NH3 in MeOH] in DCM, to give the product. This was further purified by HPLC (XBridge C18 column, 25-98% MeCN in H2O, 0.1% NH4OH) to give the title compound (58 mg, 29%). LCMS (Method 5): Rt 4.10 min, m/z 671 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.84-2.13 (6H, m), 3.46-3.50 (4H, m), 3.81-3.92 (4H, m), 4.81-4.85 (1H, m), 5.52 (1H, t, J=4.4 Hz), 6.33 (1H, s), 6.94 (1H, dd, J=8.5, 2.4 Hz), 7.08 (1H, d, J=8.4 Hz), 7.12-7.19 (2H, m), 7.31-7.43 (4H, m), 7.43 (1H, d, J=8.5 Hz), 7.60-7.62 (2H, m), 8.12 (1H, s).

Workup

  1. extractionextracted with DCM (3×20 mL)
  2. customThe combined organics were dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by FCC
  5. customto give the product
  6. customThis was further purified by HPLC (XBridge C18 column, 25-98% MeCN in H2O, 0.1% NH4OH)

Sources & evidence

ORD record
ord-0e88d8d462044d69be656b7024f2dbf8
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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