Diisopropylethylamine → HCID 178431866, compound

HRID 58303Notes

Reaction equation

[NH2:1][C@H:2]([C:4]1[N:5]=[C:6]2[S:20][CH:19]=[C:18]([CH3:21])[N:7]2[C:8](=[O:17])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1)[CH3:3].[NH2:22][C:23]1[N:31]=[C:30]2[C:26]([NH:27][CH:28]=[N:29]2)=[C:25](Br)[N:24]=1.C(N(CC)C(C)C)(C)C>C(O)CCC>[NH2:22][C:23]1[N:31]=[C:30]2[C:26]([N:27]=[CH:28][NH:29]2)=[C:25]([NH:1][C@H:2]([C:4]2[N:5]=[C:6]3[S:20][CH:19]=[C:18]([CH3:21])[N:7]3[C:8](=[O:17])[C:9]=2[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[CH3:3])[N:24]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 7-[(1S)-1-aminoethyl]-6-(3-fluorophenyl)-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.10 g, 0.33 mmol) and 2-amino-6-bromopurine (0.11 g, 0.49 mmol) in 1-butanol (0.66 mL) was treated with N,N-diisopropylethylamine (86 μL, 0.49 mmol), degassed with nitrogen for 5 min and heated at 100° C. for 18 hours. The reaction was not complete and was, therefore, heated at 115° C. for an additional 5 hours. The reaction mixture was diluted with methanol (10 mL), stirred, and filtered. The filtrate was purified by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (27 mg, 19%) as a white solid. LCMS for C20H18FN8OS (M+H)+: m/z=437.0.

Workup

customdegassed with nitrogen for 5 min
temperatureheated at 115° C. for an additional 5 hours
additionThe reaction mixture was diluted with methanol (10 mL)
filtrationfiltered
customThe filtrate was purified by RP-HPLC (XBridge C18 column
washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record: ord-fcb69ff54468406c9d81b23d6312234e
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434746B2

Reaction notes

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