Diisopropylethylamine → 2-(1H-Benzo[d]imidazol-1-yl)-N-((R)-8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine

HRID 1363134Notes

Reaction equation

F[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1OCC[C@H]2N.Cl[C:14]1[N:19]=C(Cl)C([N+]([O-])=O)=C[N:15]=1.CCN(C(C)C)C(C)C.Cl[C:34]1[N:39]=[C:38]([NH:40][C@H:41]2[C:50]3[C:45](=[C:46]([F:51])[CH:47]=[CH:48][CH:49]=3)[O:44][CH2:43][CH2:42]2)[C:37]([N+:52]([O-:54])=[O:53])=[CH:36][N:35]=1>C1COCC1>[N:15]1([C:34]2[N:39]=[C:38]([NH:40][C@H:41]3[C:50]4[C:45](=[C:46]([F:51])[CH:47]=[CH:48][CH:49]=4)[O:44][CH2:43][CH2:42]3)[C:37]([N+:52]([O-:54])=[O:53])=[CH:36][N:35]=2)[C:6]2[CH:5]=[CH:4][CH:3]=[CH:2][C:11]=2[N:19]=[CH:14]1

Participants

Conditions

Temperature: -78 °C

Procedure

(R)-8-fluorochroman-4-amine (60 mg, Example 29) was added to a solution of 2,4-dichloro-5-nitropyrimidine (70 mg) and DIEA (0.14 mL) in THF (5 mL) at −78° C. The reaction mixture was stirred for a further 15 min at −78° C. then removed from the cold bath and allowed to warm to RT. A one molar solution of the sodium salt of benzimidazole (0.7 ml, stock solution prepared via the addition of sodium hydride to a benzimidazole solution in THF) was added to the reaction intermediate ((R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine) and the resulting mixture was stirred at RT overnight. Purification via column chromatography (elution with 1 MeOH/DCM) gave the titled compound (120 mg), MH+=407.

Workup

customthen removed from the cold bath
temperatureto warm to RT
customA one molar solution of the sodium salt of benzimidazole (0.7 ml, stock solution prepared via the addition of sodium hydride to a benzimidazole solution in THF)
stirringthe resulting mixture was stirred at RT overnight
customPurification
washvia column chromatography (elution with 1 MeOH/DCM)

Sources & evidence

ORD record: ord-2e1923ff88af41a9beac9615a5acfd41
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07884109B2

Reaction notes

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