Diisopropylethylamine → HCID 178461885, compound

HRID 216795Notes

Reaction equation

HRID 216795 reaction equation
C(OC1C=CC(F)=CC=1C1C(CN)=CC2C(=C(Cl)C=CC=2)N=1)C1C=CC=CC=1.CCN(C(C)C)C(C)C.ClC1N=CN=C2C=1NC=N2.N1C(N)=C2C(NC=N2)=NC=1.[Cl:58][C:59]1[CH:60]=[CH:61][CH:62]=[C:63]2[C:68]=1[N:67]=[C:66]([C:69]1[CH:74]=[CH:73][CH:72]=[C:71]([F:75])[CH:70]=1)[C:65]([C@H:76]([NH:78][C:79]1[N:87]=[CH:86][N:85]=[C:84]3[C:80]=1[N:81]=[CH:82][NH:83]3)[CH3:77])=[CH:64]2>C(O)CCC>[Cl:58][C:59]1[CH:60]=[CH:61][CH:62]=[C:63]2[C:68]=1[N:67]=[C:66]([C:69]1[CH:74]=[CH:73][CH:72]=[C:71]([F:75])[CH:70]=1)[C:65]([C@@H:76]([NH:78][C:79]1[N:87]=[CH:86][N:85]=[C:84]3[C:80]=1[N:81]=[CH:82][NH:83]3)[CH3:77])=[CH:64]2

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 53592776-ChloropurineHCID 57707788HCID 57707788, compoundHCID 178461884HCID 178461884, compoundHCID 178508693HCID 178508693, compound

Product 1

HCID 178461885HCID 178461885, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of (2-(2-(benzyloxy)-5-fluorophenyl)-8-chloroquinolin-3-yl)-methanamine (0.120 g, 0.40 mmol) in n-butanol (5 mL) was treated with DIEA (0.80 mmol, 2.0 eq) followed with 6-chloropurine (0.075 g, 0.48 mmol, 1.2 eq) at 100° C. for 8 h. The reaction mixture was concentrated and purified by column chromatography on a Redi-Sep™ column using 0 to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 as eluent to provide the mixture of N-(S)-1-(8-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)-9H-purin-6-amine and N-((R)-1-(8-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)-9H-purin-6-amine. Further separation by chiral HPLC with IA column at IPA/Hexane (10%) provides N-((S)-1-(8-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)-9H-purin-6-amine [PI3Kδ IC50=6 nM] as a white solid. 1H-NMR (MeOD) δ ppm 8.43 (s, 1H), 8.05 (s, 1H), 7.98 (s, 1H), 7.73-7.80 (m, 2H), 7.48-7.53 (m, 1H), 7.44-7.49 (m, 1H), 7.35-7.44 (m, 2H), 7.04-7.11 (m, 1H), 1.44-1.47 (d, 3H), Mass Spectrum (ESI) m/e=419 (M+1), and N—((R)-1-(8-chloro-2-(3-fluorophenyl)-quinolin-3-yl)ethyl)-9H-purin-6-amine [PI3Kδ IC50=424 nM] as a white solid. 1H-NMR (MeOD) δ ppm, 8.56 (s, 1H), 8.17 (s, 1H), 8.10 (s, 1H), 7.84-7.93 (m, 2H), 7.45-7.66 (m, 4H), 7.14-7.23 (m, 1H), 3.89-3.98 (m, 1H), 1.57-1.60 (d, 3H) Mass Spectrum (ESI) m/e=419 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by column chromatography on a Redi-Sep™ column
  3. customto provide
  4. customFurther separation by chiral HPLC with IA column at IPA/Hexane (10%)

Sources & evidence

ORD record
ord-d8174dc2852444f088958e82cbc562e3
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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