(R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine → (R)-N2-(2-(2,4-Dimethoxybenzylamino)-4-fluorophenyl)-N4-(8-fluorochroman-4-yl)-5-nitropyrimidine-2,4-diamine

HRID 1363180Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[C:18]3[C:13](=[C:14]([F:19])[CH:15]=[CH:16][CH:17]=3)[O:12][CH2:11][CH2:10]2)[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][N:3]=1.[CH3:23][O:24][C:25]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:26]=1[CH2:27][NH:28][C:29]1[C:30]([NH2:36])=[CH:31][CH:32]=[C:33]([F:35])[CH:34]=1>C(#N)C.[Cl-].[Na+].O>[CH3:23][O:24][C:25]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:26]=1[CH2:27][NH:28][C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=1[NH:36][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[C:18]3[C:13](=[C:14]([F:19])[CH:15]=[CH:16][CH:17]=3)[O:12][CH2:11][CH2:10]2)[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of (R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine (32 mg), N1-(2,4-dimethoxybenzyl)-5-fluorobenzene-1,2-diamine (28 mg) and KCO3 (41 mg) in ACN was heated at 65° C. for 3 hr, cooled to RT, diluted with brine and extracted with EtOAc (2×). The combined organics were evaporated, and purified by column chromatography (eluted with 30% EtOAc/Hex) to yield the titled product (21 mg). 1H-NMR (300 MHz, CDCl3) δ 9.0 (s, 1H), 8.6 (br d, 1H), 7.2-6.8 (m, 6H), 6.5-6.3 (m, 4H), 4.4-4.2 (m, 4H), 3.8 (s, 6H), 2.3-2.2 (m, 2H).

Workup

temperaturecooled to RT
extractionextracted with EtOAc (2×)
customThe combined organics were evaporated
custompurified by column chromatography (eluted with 30% EtOAc/Hex)

Sources & evidence

ORD record: ord-25c05c36b7e94d2e822c33fb49d2be86
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07884109B2

Reaction notes

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