Lithium Hydroxide → 2-(4-(5-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)piperazin-1-yl)acetamide

HRID 531761Notes

Reaction equation

HRID 531761 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]=[C:92]([F:94])[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:78]([NH2:80])=[O: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:94][C:92]1[CH:91]=[C:49]([CH:48]=[C:47]([F:46])[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:78]([NH2:80])=[O: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 900314972-(4-(5-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)piperazin-1-yl) acetamideHCID 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 729446462-(4-(5-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)piperazin-1-yl)acetamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, 2-(4-(5-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)piperazin-1-yl) acetamide (100 mg, 0.146 mmol) was hydrolyzed with lithium hydroxide (31 mg, 0.733 mmol) in THF/methanol/water (2/2/1 mL) to yield 28 mg (36.3% yield) of desired product. 1H NMR (CD3OD, 300 MHz): δ 8.53-8.48 (m, 3H), 8.259-8.257 (d, 1H), 8.15-8.05 (dd, 1H), 7.988-7.986 (d, 1H), 7.72 (s, 1H), 7.19-7.10 (d, 1H), 6.90-6.82 (m, 3H), 5.43 (s, 2H), 4.05-3.90 (m, 6H), 3.51-3.49 (t, 4H). MS: m/z=529.2 (M+1), HPLC: 98.61% in method A.

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-1dc67b0c3aa247e685f1b8b5e0a0228d
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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