4,6-Dichloro-5-nitropyrimidine → HCID 86687801, compound

HRID 1427416Notes

Reaction equation

HRID 1427416 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.C1CCN2C(=NCCC2)CC1.[Cl:31][C:32]1[C:37]([N+:38]([O-:40])=[O:39])=[C:36](Cl)[N:35]=[CH:34][N:33]=1>CC#N>[Cl:31][C:32]1[N:33]=[CH:34][N:35]=[C:36]([O:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:4][CH:3]=2)[C:37]=1[N+:38]([O-:40])=[O:39]

Participants

5

Reactant 3

HCID 203124,6-Dichloro-5-nitropyrimidineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10923237tert-Butyl (4-hydroxynaphthalen-1-yl)carbamate

Product 1

HCID 86687801HCID 86687801, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of tert-butyl (4-hydroxynaphthalen-1-yl)carbamate (20.0 g, 73.0 mmol) in MeCN (200 mL) under N2 was added DBU (13 mL, 87 mmol) and after 1 hr at RT the resulting mixture was treated dropwise with a solution of 4,6-dichloro-5-nitropyrimidine (15.5 g, 80.0 mmol) in MeCN (150 mL). After 2.5 hr at RT the mixture was evaporated in vacuo and the residue was triturated with DCM (150 mL) and isohexane (200 mL). The insoluble residue was separated and set aside and the triturant was evaporated in vacuo. The residue so obtained was partitioned between DCM (200 mL) and sat aq NaHCO3 (200 mL) and the organic layer was separated and evaporated in vacuo. The residue was triturated with EtOAc to give an off white solid (batch 1). The EtOAc triturant was concentrated in vacuo to ˜20 mL and the precipitate which formed was isolated by filtration and washed with EtOAc to afford a second batch of same material, also as an off white solid. The first and second batches of product were combined to afford tert-butyl (4-((6-chloro-5-nitropyrimidin-4-yl)oxy)naphthalen-1-yl)carbamate (10.4 g, 34%); Rt 2.69 min (Method 2); m/z 439/441 (M+Na)+ (ES+).

Workup

  1. customAfter 2.5 hr at RT the mixture was evaporated in vacuo
  2. customthe residue was triturated with DCM (150 mL) and isohexane (200 mL)
  3. customThe insoluble residue was separated
  4. customthe triturant was evaporated in vacuo
  5. customThe residue so obtained
  6. customwas partitioned between DCM (200 mL)
  7. customthe organic layer was separated
  8. customevaporated in vacuo
  9. customThe residue was triturated with EtOAc
  10. customto give an off white solid (batch 1)
  11. concentrationThe EtOAc triturant was concentrated in vacuo to ˜20 mL
  12. customthe precipitate which formed
  13. customwas isolated by filtration
  14. washwashed with EtOAc
  15. customto afford a second batch of same material

Sources & evidence

ORD record
ord-89ebbdb797af4683abab522c592fe337
Source dataset
uspto-grants-2015_01
Patent number
US08933228B2

Reaction notes

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