Lithium Hydroxide → HCID 71558549, compound

HRID 1411924Notes

Reaction equation

HRID 1411924 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:33]2[C:45](=[O:46])[C:44]3[S:43][C:42]4[CH2:41][CH2:40][CH2:39][CH2:38][C:37]=4[C:36]=3[CH:35]=[N:34]2)=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:30]=[C:22]3[CH2:23][N:24]([C:27](=[O:29])[CH3:28])[CH2:25][CH2:26][N:21]3[N:20]=2)[C:15](=[O:31])[N:14]([CH3:32])[CH:13]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[C:27]([N:24]1[CH2:25][CH2:26][N:21]2[N:20]=[C:19]([NH:18][C:16]3[C:15](=[O:31])[N:14]([CH3:32])[CH:13]=[C:12]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([N:33]5[C:45](=[O:46])[C:44]6[S:43][C:42]7[CH2:41][CH2:40][CH2:39][CH2:38][C:37]=7[C:36]=6[CH:35]=[N:34]5)[C:6]=4[CH2:5][OH:4])[CH:17]=3)[CH:30]=[C:22]2[CH2:23]1)(=[O:29])[CH3:28]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86684471HCID 86684471, compound

Product 1

HCID 71558549HCID 71558549, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 22722550Tetrahydrofuran water isopropanolSolvent

Conditions

Temperature
35 °C

Procedure

A mixture of {4-[5-({5-acetyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridin-3-yl}methyl acetate 247a (100 mg, 0.16 mmol) and lithium hydroxide (96 mg, 4.0 mmol) in i-propanol/THF/water (2:2:1, 10 mL) was stirred at 35° C. for 30 min. The mixture was concentrated under reduced pressure. To the residue was added water (5 mL) and the resulting mixture was extracted with dichloromethane three times. The combined organic layer was then concentrated under reduced pressure and the resulting residue was purified by reverse-phase prep-HPLC to afford 247 (51 mg, 53%). MS-ESI: [M+H]+ 599.3. 1H NMR (500 MHz, DMSO-d6, T=80° C.) δ 8.54-8.51 (m, 1H), 8.38 (d, J=3.0 Hz, 1H), 7.93-7.91 (m, 2H), 7.48 (d, J=8.5 Hz, 1H), 7.35 (d, J=3.0 Hz, 1H), 6.00 (s, 1H), 4.64-4.62 (m, 2H), 4.39 (s, 2H), 3.98-3.95 (m, 2H), 3.89-3.86 (m, 2H), 3.58 (s, 3H), 2.95-2.93 (m, 2H), 2.87-2.84 (m, 2H), 2.08 (s, 3H), 1.89-1.87 (m, 4H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionTo the residue was added water (5 mL)
  3. extractionthe resulting mixture was extracted with dichloromethane three times
  4. concentrationThe combined organic layer was then concentrated under reduced pressure
  5. customthe resulting residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-e456a86c4c3c42709650f305d7f4c4db
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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