2,4-Dichloropyrimidine → 2-((S)-1-phenylethylamino)-4-(5-(2-chloropyrimidin-4-yl)aminobenzimidazol-1-yl)pyrimidine

HRID 2300893Notes

Reaction equation

[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([NH2:25])=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.[Cl:35][C:36]1[N:41]=[C:40](Cl)[CH:39]=[CH:38][N:37]=1>CN(C=O)C>[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([NH:25][C:38]5[CH:39]=[CH:40][N:41]=[C:36]([Cl:35])[N:37]=5)=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-[(S)-1-phenylethylamino]-4-[5-aminobenzimidazol-1-yl]pyrimidine (45.9 mg) in DMF (2 mL) was added diisopropylethylamine (73 μL) followed by 2,4-dichloropyrimidine (24.9 mg). The resulting solution was heated to 100° C. for 16 h then the mixture concentrated in vacuo. This crude was purified on silica gel (2-5%(2M NH3 in MeOH)/CH2Cl2) to yield 18.3 mg of 2-((S)-1-phenylethylamino)-4-(5-(2-chloropyrimidin-4-yl)aminobenzimidazol-1-yl)pyrimidine (L-860,182). 1H NMR (500 MHz, CDCl3, partial): δ 8.51 (br s, 1H); 8.42 (d, J=5.5 Hz, 1H); 8.13 (d, J=5.9 Hz, 1H); 7.75 (s, 1H); 7.45 (d, J=7.3 Hz, 2H); 7.40 t, J=7.7 Hz, 2H); 6.77 (d, J=5.3 Hz, 1H); 6.56 (d, J=6.0 Hz, IH); 1.66 (d, J=6.9 Hz, 3H). Mass spectrum (ESI) 443.3 (M+1).

Workup

concentrationthe mixture concentrated in vacuo
customThis crude was purified on silica gel (2-5%(2M NH3 in MeOH)/CH2Cl2)

Sources & evidence

ORD record: ord-f48dafbf3661442ca5d26c64d36c16a0
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06498165B1

Reaction notes

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