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

HRID 531766Notes

Reaction equation

HRID 531766 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:66]=[CH:67][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)=[N:69][CH:70]=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)=[N:69][CH:70]=4)[CH:63]=3)[NH:58][CH:57]=2)[CH:53]=[N:52]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 90030742(S)-1-(4-(5-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)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 90030815(S)-1-(4-(5-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl) piperazin-1-yl)propan-2-olYield 75.3%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (S)-1-(4-(5-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)piperazin-1-yl) propan-2-ol (90 mg, 0.135 mmol) was hydrolyzed with lithium hydroxide (14 mg, 0.270 mmol) in THF/methanol/water (5/2/1 mL) to yield 52 mg (63.0% yield) of desired product. 1H NMR (CD3OD, 400 MHz): δ 8.56-8.55 (d, 1H), 8.485-8.481 (d, 1H), 8.44-8.43 (d, 1H), 8.24 (s, 1H), 8.09-8.06 (dd, 1H), 7.98 (s, 1H), 7.71 (s, 1H), 7.40-7.38 (q, 1H), 7.13-7.11 (m, 2H), 7.10-7.00 (m, 2H), 5.45 (s, 2H), 4.70-4.40 (bs, 2H), 4.30-4.20 (m, 1H), 3.90-3.50 (bs, 4H), 3.17-3.11 (m, 2H), 1.30-1.27 (m, 3H). MS: m/z=512.3 (M+1), HPLC: 98.72% in method A.

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-a37fe51ded3e46e3b5a8b46938ab9a14
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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