Diisopropylethylamine → HCID 86677060, compound

HRID 1626918Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[NH2:12][C@H:13]([C:15]1[N:16]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:17](=[O:26])[C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][C:19]=2[Cl:25])[CH3:14].CCN(C(C)C)C(C)C>C1COCC1.C(Cl)Cl>[Cl:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:18]=1[C:17](=[O:26])[N:16]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:15]([C@@H:13]([NH:12][C:6]1[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=1)[CH3:14])=[CH:24]2

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 2,4-dichloro-5-nitropyrimidine (250 mg, 1.29 mmol, 1.15 eq.) in THF (2 mL) was chilled in a −78° C. bath. To this solution was slowly added over 40 mins a mixture of compound 1 (335 mg, 1.12 mmol, 1.0 eq.) and DIEA (450 μL, 2.58 mmol, 2.3 eq.) in THF (4 mL). After addition was complete, the reaction was stirred at −78° C. during 30-40 mins, then allowed to warm slowly to 15° C. over 1 h. The reaction mixture was diluted with DCM (40 mL), washed with water and brine (15 mL each), dried over Na2SO4, and concentrated. This residue was purified by flash chromatography eluting with 300 mL each 10/20/30/40% EtOAc/hexanes to give (S)-8-chloro-3-(1-(2-chloro-5-nitropyrimidin-4-ylamino)ethyl)-2-phenylisoquinolin-1(2H)-one 75. ESI-MS 456.15 [M+H]+.

Workup

additionTo this solution was slowly added over 40 mins
additionAfter addition
temperatureto warm slowly to 15° C. over 1 h
washwashed with water and brine (15 mL each)
dry with materialdried over Na2SO4
concentrationconcentrated
customThis residue was purified by flash chromatography
washeluting with 300 mL each 10/20/30/40% EtOAc/hexanes

Sources & evidence

ORD record: ord-7023ca60d0094f22829c439a391a49fd
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785470B2

Reaction notes

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