4,6-Dichloro-5-nitropyrimidine → 6-chloro-N-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-5-nitropyrimidin-4-amine

HRID 1848014Notes

Reaction equation

HRID 1848014 reaction equation
[CH3:1][C:2]1([CH3:22])[N:6]([C:7]2[S:8][C:9]3[CH:15]=[C:14]([CH2:16][NH2:17])[CH:13]=[CH:12][C:10]=3[N:11]=2)[C@@H:5]2[CH2:18][CH2:19][CH2:20][CH2:21][C@H:4]2[O:3]1.CCN(C(C)C)C(C)C.[Cl:32][C:33]1[C:38]([N+:39]([O-:41])=[O:40])=[C:37](Cl)[N:36]=[CH:35][N:34]=1>>[Cl:32][C:33]1[N:34]=[CH:35][N:36]=[C:37]([NH:17][CH2:16][C:14]2[CH:13]=[CH:12][C:10]3[N:11]=[C:7]([N:6]4[C@@H:5]5[CH2:18][CH2:19][CH2:20][CH2:21][C@H:4]5[O:3][C:2]4([CH3:22])[CH3:1])[S:8][C:9]=3[CH:15]=2)[C:38]=1[N+:39]([O-:41])=[O:40]

Participants

4

Reactant 3

HCID 203124,6-Dichloro-5-nitropyrimidineHCID 81531DiisopropylethylamineHCID 86681035(2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methanamine

Product 1

HCID 866810366-chloro-N-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-5-nitropyrimidin-4-amineYield 46%

Procedure

To a stirred mixture of (2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methanamine (236 mg, 0.7 mmol) from Step 4 of this Example and DIEA (388 μL, 2.2 mmol) at 0° C. under argon was added 4,6-dichloro-5-nitropyrimidine (159 mg, 0.8 mmol) in one portion. The mixture was stirred for 4 h and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (eluting with a gradient of 100% hexanes to 50% EtOAc in hexanes) to afford 6-chloro-N-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-5-nitropyrimidin-4-amine (153 mg, 43%) as an oil. 1H NMR (300 MHz, CDCl3) δ 8.45 (s, 1H), 7.81 (br s, 1H), 7.57-7.63 (m, 2H), 7.22-7.31 (m, 1H), 4.85 (d, J=5.7 Hz, 2H), 3.11 (m, 1H), 2.82 (m, 1H), 2.11-2.16 (m, 1H), 1.90 (m, 1H), 1.80 (s, 3H), 1.51-1.69 (m, 5H), 1.19-1.49 (m, 4H). LCMS (ESI) m/z 475 (M+H)+.

Workup

  1. customat 0° C.
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by silica gel flash chromatography (
  4. washeluting with a gradient of 100% hexanes to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d67ca680c0ce4899bc76c54d01d19425
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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