Lithium Hydroxide → HCID 71558549, compound

HRID 592986Notes

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

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

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

Sources & evidence

ORD record: ord-e691e108158c4173b2f2cd76bb8b2039
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238655B2

Reaction notes

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