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

HRID 531747Notes

Reaction equation

HRID 531747 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:92]=[CH:93][CH:94]=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)[CH:53]=[N:52]1.[OH-].[Li+]>C1COCC1.CO.O>[F:46][C:47]1[CH:48]=[C:49]([CH:92]=[CH:93][CH:94]=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)[CH:53]=[N:52]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 90031214(S)-1-(4-(4-(3-(1-(3-fluorobenzyl)-5-methyl-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 90031319(S)-1-(4-(4-(3-(1-(3-fluorobenzyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-olYield 6.4%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (S)-1-(4-(4-(3-(1-(3-fluorobenzyl)-5-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-ol (200 mg, 0.29 mmol) was hydrolyzed with lithium hydroxide (37 mg, 0.88 mmol) in THF/methanol/water (6/4/2 mL) to yield 10 mg (6.4% yield) after purification by preparative HPLC along with one more isomer example 130. 1H NMR (CDCl3, 300 MHz): δ 9.12 (s, 1H), 8.548-8.542 (d, 1H), 8.02-8.01 (d, 1H), 7.59 (s, 1H), 7.54-7.51 (d, 2H), 7.36-7.29 (m, 2H), 7.26-6.91 (m, 5H), 5.32 (s, 2H), 3.95-3.90 (m, 1H), 3.30-3.23 (m, 4H), 2.90-2.86 (m, 2H), 2.62-2.60 (m, 2H), 2.43-2.31 (m, 5H), 1.19-1.17 (d, 3H). MS: m/z=524.9 (M+1), HPLC: 95.68% in method A.

Workup

  1. customreaction conditions
  2. customto yield 10 mg (6.4% yield)
  3. customafter purification by preparative HPLC along with one more isomer example 130

Sources & evidence

ORD record
ord-ee3d993445ae471084e38dad676a5f81
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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