Lithium Hydroxide → (S)-1-(4-(2-fluoro-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 531703Notes

Reaction equation

HRID 531703 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:52]=[C:51]([C:53]2[CH:54]=[C:55]3[C:61]([C:62]4[CH:63]=[N:64][N:65]([CH2:67][C:68]5[CH:73]=[CH:72][CH:71]=[C:70]([F:74])[CH:69]=5)[CH:66]=4)=[CH:60][N:59](S(C4C=CC(C)=CC=4)(=O)=O)[C:56]3=[N:57][CH:58]=2)[CH:50]=[CH:49][C:48]=1[N:85]1[CH2:90][CH2:89][N:88]([CH2:91][C@@H:92]([OH:94])[CH3:93])[CH2:87][CH2:86]1.[OH-].[Li+]>C1COCC1.CO.O>[F:46][C:47]1[CH:52]=[C:51]([C:53]2[CH:54]=[C:55]3[C:61]([C:62]4[CH:63]=[N:64][N:65]([CH2:67][C:68]5[CH:73]=[CH:72][CH:71]=[C:70]([F:74])[CH:69]=5)[CH:66]=4)=[CH:60][NH:59][C:56]3=[N:57][CH:58]=2)[CH:50]=[CH:49][C:48]=1[N:85]1[CH2:90][CH2:89][N:88]([CH2:91][C@@H:92]([OH:94])[CH3:93])[CH2:87][CH2:86]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 90033580(S)-1-(4-(2-fluoro-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 90031565(S)-1-(4-(2-fluoro-4-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)propan-2-olYield 58.4%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (S)-1-(4-(2-fluoro-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 (100 mg, 0.146 mmol) was hydrolyzed with lithium hydroxide (30 mg, 0.73 mmol) in THF/methanol/water (2/2/1 mL) to yield 45 mg (58.4% yield) of desired product. 1H NMR (CD3OD, 400 MHz): δ 8.54 (s, 2H), 8.27 (s, 1H), 7.98 (s, 1H), 7.74 (s, 1H), 7.60-7.53 (m, 2H), 7.45-7.35 (q, 1H), 7.25-7.21 (t, 1H), 7.14-7.12 (d, 1H), 7.09-7.00 (m, 2H), 5.45 (s, 2H), 4.30-4.20 (m, 1H), 3.76-3.55 (m, 4H), 3.50-3.30 (m, 2H), 3.29-3.15 (m, 4H), 1.29-1.27 (d, 3H). MS: m/z=529.6 (M+1), HPLC: 98.28% in method A.

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-f4c4a92279f64e3b8d2dbf1881e0003d
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

Loading…