Diisopropylethylamine → (R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine

HRID 1363179Notes

Reaction equation

Cl.[F:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][CH2:10][CH2:9][C@H:8]2[NH2:13].CCN(C(C)C)C(C)C.[Cl:23][C:24]1[N:29]=[C:28](Cl)[C:27]([N+:31]([O-:33])=[O:32])=[CH:26][N:25]=1>C(Cl)Cl>[Cl:23][C:24]1[N:29]=[C:28]([NH:13][C@H:8]2[C:7]3[C:12](=[C:3]([F:2])[CH:4]=[CH:5][CH:6]=3)[O:11][CH2:10][CH2:9]2)[C:27]([N+:31]([O-:33])=[O:32])=[CH:26][N:25]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of (R)-8-fluorochroman-4-amine hydrochloride (1.02 g) and DIEA (2.6 mL) in DCM (10 mL) was slowly added to a solution of 2,4-dichloro-5-nitropyrimidine (0.97 g) THF (25 mL) at −78° C. The reaction mixture was stirred for 30 min at −78° C. then allowed to warm to RT overnight. The reaction was quenched with the addition of sat. NH4Cl (1 mL), the solvent volume was reduced in vacuo, and the resulting mixture partition between EtOAc and water then separated. The crude material was purified via column chromatography, elution with 30% EtOAc/Hex gave the titled product (1.43 g). 1H-NMR (300 MHz, CDCl3) δ 9.1 (s, 1H), 8.6 (br d, 1H), 7.1-6.8 (m, 3H), 5.6 (dd, 1H), 4.4 (m 1H), 4.3 (m, 1H), 2.4 (m, 1H), 2.2 (m, 1H).

Workup

temperatureto warm to RT overnight
customThe reaction was quenched with the addition of sat. NH4Cl (1 mL)
customthe resulting mixture partition between EtOAc and water
customthen separated
customThe crude material was purified via column chromatography, elution with 30% EtOAc/Hex

Sources & evidence

ORD record: ord-69e05166bdca431d830b335cd44f90bb
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07884109B2

Reaction notes

Loading…