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

HRID 531733Notes

Reaction equation

HRID 531733 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:93]=[CH:94][CH:95]=1)[CH2:50][N:51]1[C:55]([CH3:56])=[C:54]([C:57]2[C:65]3[C:60](=[N:61][CH:62]=[C:63]([C:66]4[CH:71]=[CH:70][C:69]([N:72]5[CH2:77][CH2:76][N:75]([CH2:78][C@@H:79]([OH:81])[CH3:80])[CH2:74][CH2:73]5)=[CH:68][CH:67]=4)[CH:64]=3)[N:59](S(C3C=CC(C)=CC=3)(=O)=O)[CH:58]=2)[C:53]([CH3:92])=[N:52]1.[OH-].[Li+]>C1COCC1.CO.O>[F:46][C:47]1[CH:48]=[C:49]([CH:93]=[CH:94][CH:95]=1)[CH2:50][N:51]1[C:55]([CH3:56])=[C:54]([C:57]2[C:65]3[C:60](=[N:61][CH:62]=[C:63]([C:66]4[CH:67]=[CH:68][C:69]([N:72]5[CH2:77][CH2:76][N:75]([CH2:78][C@@H:79]([OH:81])[CH3:80])[CH2:74][CH2:73]5)=[CH:70][CH:71]=4)[CH:64]=3)[NH:59][CH:58]=2)[C:53]([CH3:92])=[N:52]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 90031229(2S)-1-(4-(4-(3-(1-(3-fluorobenzyl)-3,5-dimethyl-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 72944538(2S)-1-(4-(4-(3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-olYield 24.2%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (2S)-1-(4-(4-(3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-ol (165 mg, 0.238 mmol) was hydrolyzed with lithium hydroxide (100 mg, 2.38 mmol) in THF/methanol/water (20/10/5 mL) to yield 31 mg (13% yield) of desired product. 1H NMR (CD3OD, 300 MHz): δ 8.43-8.42 (d, 1H), 7.838-7.831 (d, 1H), 7.50-7.57 (d, 2H), 7.40-7.30 (m, 2H), 7.05-6.95 (m, 4H), 6.95-6.84 (m, 1H), 5.35 (s, 2H), 4.05-3.95 (m, 1H), 3.25-3.22 (t, 4H), 2.80-2.62 (m, 4H), 2.50-2.30 (m, 2H), 2.20 (s, 3H), 2.16 (s, 3H), 1.17-1.15 (d, 3H). MS: m/z=538.9 (M+1), HPLC: 95.51% in method A.

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-51e7aaed0460482eaf682e1c2fe59309
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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