Diisopropylethylamine → (R)-methyl 4-(4-((1-(1,3,4-oxadiazol-2-yl)propyl)(cyclopentyl)amino)-5-nitropyrimidin-2-ylamino)-3-methoxybenzoate

HRID 476132Notes

Reaction equation

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

Participants

Conditions

Temperature: 140 °C

Procedure

2-chloro-N-cyclopentyl-5-nitro-N-[(1R)-1-(1,3,4-oxadiazol-2-yl)propyl]pyrimidin-4-amine (61.5 mg, 0.1743 mmol) and methyl 4-amino-3-methoxy benzoate (37.9 mg, 0.2092 mmol) in 4-methylpentan-2-ol (600 L) were treated with DIPEA (33.8 mg, 45.6 mL, 0.2614 mmol) and the reaction mixture stirred at 140° C. for 4 hours. The reaction mixture was concentrated in vacuo and the residue purified by column chromatography (50% EtOAc/Petrol) to give the sub-title compound as a brown oil (42 mg, 48%); 1H NMR (400.0 MHz, DMSO) d 0.75-0.89 (3H, m), 1.15-1.75 (8H, m), 2.24-2.34 (1H, m), 2.40-2.51 (1H, m), 2.61-2.72 (1H, m), 3.55-3.63 (1H, m), 3.84 (3H, s), 3.89 (3H, s), 7.44 (1H, s), 7.55-7.65 (2H, m), 7.75-8.03 (1H, br s), 8.12 (1H, s), 8.77 (1H, s); MS ES(+) 498.1.

Workup

concentrationThe reaction mixture was concentrated in vacuo
customthe residue purified by column chromatography (50% EtOAc/Petrol)

Sources & evidence

ORD record: ord-360a1c6af6d044bc86fdaa838dad76a8
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637666B2

Reaction notes

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