tert-butyl (S)-6-hydroxy-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate → (R)-1-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridine-1-yl)pyridin-2-yl)-1,4-diazepan-6-ol

HRID 57901Notes

Reaction equation

HRID 57901 reaction equation
[OH:1][C@@H:2]1[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6][CH2:5][N:4]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N:22]3[C:30]4[CH:29]=[C:28]([C:31]5[CH:32]=[N:33][N:34]([CH2:36][C:37]([F:40])([F:39])[F:38])[CH:35]=5)[N:27]=[CH:26][C:25]=4[CH:24]=[N:23]3)[N:17]=2)[CH2:3]1>Cl.CO>[F:40][C:37]([F:38])([F:39])[CH2:36][N:34]1[CH:35]=[C:31]([C:28]2[N:27]=[CH:26][C:25]3[CH:24]=[N:23][N:22]([C:18]4[N:17]=[C:16]([N:4]5[CH2:3][C@H:2]([OH:1])[CH2:8][NH:7][CH2:6][CH2:5]5)[CH:21]=[CH:20][CH:19]=4)[C:30]=3[CH:29]=2)[CH:32]=[N:33]1

Participants

3

Reactant 1

HCID 86707093tert-butyl (S)-6-hydroxy-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

Product 1

HCID 72715622(R)-1-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridine-1-yl)pyridin-2-yl)-1,4-diazepan-6-olYield 52.6%

Reagents, catalysts & solvents 1

HCID 21893726Hydrochloride methanolSolvent

Procedure

A mixture of tert-butyl(S)-6-hydroxy-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate (70 mg, 0.13 mmol) in HCl/MeOH (4.0 M, 10 mL) was stirred at room temperature for 3 hours, which was monitored by LCMS. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The crude material was purified by reverse phase prep-HPLC to afford (R)-1-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridine-1-yl)pyridin-2-yl)-1,4-diazepan-6-ol 188 as a white solid (30 mg, 52.6%). 1H NMR (500 MHz, DMSO-d6) δ (ppm) 9.16 (s, 1H), 8.74 (s, 1H), 8.55 (s, 1H), 8.49 (s, 1H), 8.21 (s, 1H), 7.69 (t, J=16 Hz, 1H), 7.17 (d, J=7.5 Hz, 1H), 6.66 (d, J=8 Hz, 1H), 5.18-5.24 (m, 2H), 4.93 (d, J=5.5 Hz, 1H), 3.96 (t, J=8.5 Hz, 1H), 3.88 (m, 2H), 3.56-3.64 (m, 2H), 2.98 (t, J=10.5 Hz, 2H), 2.80-2.84 (m, 1H), 2.64-2.72 (m, 1H); MS (ESI) m/z: 459 [M+H]+.

Workup

  1. customAfter completion of the reaction
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe crude material was purified by reverse phase prep-HPLC

Sources & evidence

ORD record
ord-5e8e2bae6a6c4a77bfd9d19e0fcfe132
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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