Lithium Hydroxide → HCID 72944858, compound

HRID 531876Notes

Reaction equation

HRID 531876 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[C:48]([N:85]2[CH2:90][CH2:89][N:88]([CH2:91][C@H:92]([OH:94])[CH3:93])[CH2:87][CH2:86]2)=[N:49][CH:50]=[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:52]=1.[OH-].[Li+]>C1COCC1.CO.O>[F:46][C:47]1[C:48]([N:85]2[CH2:90][CH2:89][N:88]([CH2:91][C@H:92]([OH:94])[CH3:93])[CH2:87][CH2:86]2)=[N:49][CH:50]=[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:52]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 118524049HCID 118524049, compoundHCID 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 72944858HCID 72944858, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Using similar reaction conditions as described in step-iii of example-1, (R)-1-(4-(3-fluoro-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 (146 mg, 0.213 mmol) was hydrolyzed with lithium hydroxide (89 mg, 2.137 mmol) in THF/methanol/water (12/4/4 mL) to yield 64 mg (57% yield) after purification by prep TLC using 8% methanol in chloroform as eluent. 1H NMR (CD3OD, 300 MHz): δ 8.45-8.44 (d, 1H), 8.35-8.32 (m, 2H), 8.32 (s, 1H), 7.94 (s, 1H), 7.83-7.78 (dd, 1H), 7.65 (s, 1H), 7.40-7.33 (m, 1H), 7.12-7.00 (m, 3H), 5.43 (s, 2H), 4.02-3.95 (m, 1H), 3.56-3.53 (t, 4H), 2.77-2.63 (m, 4H), 2.47-2.33 (m, 2H), 1.18-1.16 (d, 3H). MS: m/z=530.2 (M+1), HPLC: 98.70% in method A.

Workup

  1. customreaction conditions
  2. customto yield 64 mg (57% yield)
  3. customafter purification by prep TLC

Sources & evidence

ORD record
ord-e3685513cecd4e12bd835239baf05cc9
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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