Lithium Hydroxide → (R)-1-(4-(4-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl) piperazin-1-yl)propan-2-ol

HRID 531724Notes

Reaction equation

HRID 531724 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.[F:46][C:47]1[CH:48]=[C:49]([CH:91]=[CH:92][CH:93]=1)[CH2:50][N:51]1[CH:55]=[C:54]([C:56]2[C:64]3[C:59](=[N:60][CH:61]=[C:62]([C:65]4[CH:70]=[CH:69][C:68]([N:71]5[CH2:76][CH2:75][N:74]([CH2:77][C@H:78]([OH:80])[CH3:79])[CH2:73][CH2:72]5)=[CH:67][CH:66]=4)[CH:63]=3)[N:58](S(C3C=CC(C)=CC=3)(=O)=O)[CH:57]=2)[CH:53]=[N:52]1.[OH-].[Li+]>C1COCC1.CO.O>[F:46][C:47]1[CH:48]=[C:49]([CH:91]=[CH:92][CH:93]=1)[CH2:50][N:51]1[CH:55]=[C:54]([C:56]2[C:64]3[C:59](=[N:60][CH:61]=[C:62]([C:65]4[CH:66]=[CH:67][C:68]([N:71]5[CH2:72][CH2:73][N:74]([CH2:77][C@H:78]([OH:80])[CH3:79])[CH2:75][CH2:76]5)=[CH:69][CH:70]=4)[CH:63]=3)[NH:58][CH:57]=2)[CH:53]=[N:52]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 90030866(R)-1-(4-(4-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-olHCID 1185240853-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-5-(4-(piperidin-4-yl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine hydrochloride

Product 1

HCID 72944537(R)-1-(4-(4-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl) piperazin-1-yl)propan-2-olYield 28.6%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (R)-1-(4-(4-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-ol (160 mg, 0.24 mmol) was hydrolyzed by lithium hydroxide (50 mg, 1.2 mmol) in THF/methanol/water (3/2/1 ml) to afford 35 mg (28.6% yield) of the titled compound. 1H NMR (CD3OD, 300 MHz): δ 8.58-8.57 (d, 1H), 8.53 (s, 1H), 8.24 (s, 1H), 7.969-7.967 (d, 1H), 7.74 (s, 1H), 7.71-7.68 (d, 2H), 7.41-7.35 (m, 1H), 7.19-7.16 (d, 2H), 7.13-7.00 (m, 3H), 5.44 (s, 2H), 4.28-4.21 (m, 1H), 3.90-3.60 (m, 4H), 3.28-3.09 (m, 4H), 1.28-1.26 (d, 3H). MS: m/z=511.3 (M+1), HPLC: 95.39% in method B.

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-1ef4a9b5ba954b349d2b7bcb19a7e914
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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