Lithium Hydroxide → (S)-3-((4-(5-(6-(4-(2-hydroxypropyl)piperazin-1-yl)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrazol-1-yl)methyl)phenol

HRID 531801Notes

Reaction equation

HRID 531801 reaction equation
Cl.FC1C=C(C=CC=1)CN1C=C(C2C3C(=NC=C(C4C=CC(C5CCNCC5)=CC=4)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)C=N1.[OH:46][C@@H:47]([CH3:93])[CH2:48][N:49]1[CH2:54][CH2:53][N:52]([C:55]2[N:60]=[CH:59][C:58]([C:61]3[CH:62]=[C:63]4[C:69]([C:70]5[CH:71]=[N:72][N:73]([CH2:75][C:76]6[CH:77]=[C:78]([OH:82])[CH:79]=[CH:80][CH:81]=6)[CH:74]=5)=[CH:68][N:67](S(C5C=CC(C)=CC=5)(=O)=O)[C:64]4=[N:65][CH:66]=3)=[CH:57][CH:56]=2)[CH2:51][CH2:50]1.[OH-].[Li+]>C1COCC1.CO.O>[OH:46][C@@H:47]([CH3:93])[CH2:48][N:49]1[CH2:54][CH2:53][N:52]([C:55]2[N:60]=[CH:59][C:58]([C:61]3[CH:62]=[C:63]4[C:69]([C:70]5[CH:71]=[N:72][N:73]([CH2:75][C:76]6[CH:77]=[C:78]([OH:82])[CH:79]=[CH:80][CH:81]=6)[CH:74]=5)=[CH:68][NH:67][C:64]4=[N:65][CH:66]=3)=[CH:57][CH:56]=2)[CH2:51][CH2:50]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 1185240853-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-5-(4-(piperidin-4-yl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine hydrochlorideHCID 118524116(S)-3-((4-(5-(6-(4-(2-hydroxypropyl)piperazin-1-yl)pyridin-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrazol-1-yl)methyl)phenol

Product 1

HCID 90030374(S)-3-((4-(5-(6-(4-(2-hydroxypropyl)piperazin-1-yl)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrazol-1-yl)methyl)phenolYield 9%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (S)-3-((4-(5-(6-(4-(2-hydroxypropyl)piperazin-1-yl)pyridin-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrazol-1-yl)methyl)phenol (180 mg, 0.271 mmol) was hydrolyzed with lithium hydroxide (34 mg, 0.813 mmol) in THF/methanol/water (2/2/0.5 mL) to yield 12 mg (9% yield) of desired product. 1H NMR (CD3OD, 400 MHz): δ 8.51-8.45 (m, 2H), 8.32-8.31 (m, 1H), 8.16 (s, 1H), 7.99-7.92 (m, 2H), 7.20-7.16 (t, 1H), 7.06-6.97 (m, 1H), 6.78-6.69 (m, 3H), 5.36 (s, 2H), 4.70-4.60 (m, 1H), 4.26-4.20 (t, 1H), 4.10-4.05 (q, 1H), 3.78-3.70 (m, 4H), 3.58-3.49 (m, 2H), 2.92-2.61 (m, 2H), 2.63-2.61 (m, 1H), 1.22-1.21 (m, 3H). MS: m/z=510.2 (M+1), HPLC: 98.41% in method A.

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-7ed3297e844345de804b878b86197e2c
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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