Lithium Hydroxide → HCID 73603938, compound

HRID 521730Notes

Reaction equation

[F:1][C:2]1[C:3]([C:32]([OH:35])([CH3:34])[CH3:33])=[N:4][C:5]([N:8]2[CH2:16][C@@H:15]3[C@@:10]([C:26]4[CH:31]=[N:30][CH:29]=[CH:28][N:27]=4)([N:11]=[C:12]([NH:17]C(=O)C4C=CC=CC=4)[S:13][CH2:14]3)[CH2:9]2)=[N:6][CH:7]=1.[OH-].[Li+]>CO>[NH2:17][C:12]1[S:13][CH2:14][C@@H:15]2[CH2:16][N:8]([C:5]3[N:4]=[C:3]([C:32]([OH:35])([CH3:33])[CH3:34])[C:2]([F:1])=[CH:7][N:6]=3)[CH2:9][C@:10]2([C:26]2[CH:31]=[N:30][CH:29]=[CH:28][N:27]=2)[N:11]=1

Participants

Conditions

Temperature: 60 °C

Procedure

N-[(4aR,7aR)-6-[5-fluoro-4-(1-hydroxy-1-methyl-ethyl)pyrimidin-2-yl]-7a-pyrazin-2-yl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (330 mg, 0.668 mmol) is dissolved in methanol (8 mL) with stirring. Lithium hydroxide (42.51 mg, 1 mmol) is added and the reaction is heated at 60° C. for 5 hours 30 minutes. The reaction is cooled to room temperature and loaded onto a silica gel column. The column is eluted with a 0-5% gradient of 0.14 M ammonia/methanol in dichloromethane. The product obtained is further purified by preparative HPLC using a 10% B to 100% B gradient over 9 minutes at 60 mL/minute (column=Phenomenex Gemini NX C18, 30×100 mm, 5 μm. Mobile phase A: water with 10 mM ammonium bicarbonate, pH adjusted to pH 10 with ammonia. Mobile phase B: acetonitrile) to give the title compound (146 mg, 56%). ES/MS (m/e): 390 (M+1).

Workup

temperatureThe reaction is cooled to room temperature
washThe column is eluted with a 0-5% gradient of 0.14 M ammonia/methanol in dichloromethane
customThe product obtained
customis further purified by preparative HPLC
customover 9 minutes

Sources & evidence

ORD record: ord-71a18a138ded4da5b7c833117872d8a8
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328124B2

Reaction notes

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