tert-Butanol → HCID 67271357, compound

HRID 1696576Notes

Reaction equation

HRID 1696576 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8](C(O)=O)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])=CC=1.CC[N:39]([CH2:42]C)CC.[CH3:44][C:45]([OH:48])([CH3:47])[CH3:46]>CCOC(C)=O.O>[C:1]([C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:8]([NH:39][C:42](=[O:27])[O:48][C:45]([CH3:47])([CH3:46])[CH3:44])=[CH:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 67271086HCID 67271086, compound

Product 1

HCID 67271357HCID 67271357, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Using general method E, the material from the previous reaction (1.26 g, 4.70 mmol) was saponified to yield 2-t-butyl-4-phenylpyrimidine-5-carboxylic acid (1.10 g, 92% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.40 (s, 9H), 7.50-7.52 (m, 3H), 7.67-7.69 (m, 2H), 9.02 (s, 1H). 2-t-butyl-4-phenylpyrimidine-5-carboxylic acid (1.10 g, 4.29 mmol) was combined in t-BuOH (11 mL) with DPPA (1.18 g, 4.29 mmol) and Et3N (0.434 g, 4.29 mmol). The mixture was heated at reflux, stirred overnight, then cooled to RT and diluted with EtOAc (75 mL) and H2O (75 mL). The organic phase was separated, washed with brine, dried (Na2SO4) and concentrated. The resultant solid was treated with EtOAc (5 mL) and sonicated for 5 min then filtered free of solids and evaporated to a small volume and the solution purified by column chromatography to yield t-butyl 2-t-butyl-4-phenylpyrimidin-5-ylcarbamate (1.2 g, 85% yield) as a white foam. LC-MS (EI) m/z: 328.3 (M+H+). This material (1.02 g, 3.0 mmol) was dissolved in CH2Cl2 (10 mL) and treated with 3N HCl/EtOAc (10 mL), stirred at RT and subsequently treated with additional 3N HCl/EtOAc (5 mL) and then concentrated to yield 2-t-butyl-4-phenylpyrimidin-5-amine hydrochloride as a yellow solid (0.724 g, 88%). LC-MS (EI) m/z: 228.2 (M+H+). Using general method A, this material (120 mg, 0.455 mmol) and 1,2-dichloro-3-isocyanatobenzene (94 mg, 0.500 mmol) were combined to yield 1-(2-t-butyl-4-phenylpyrimidin-5-yl)-3-(2,3-dichlorophenyl)urea (45 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6): δ 1.39 (s, 9H), 7.29-7.34 (m, 2H), 7.53-7.59 (m, 3H), 7.77-7.79 (m, 2H), 8.06-8.08 (m, 1H), 8.20 (s, 1H), 8.98-9.02 (m, 2H); LC-MS (EI) m/z: 417.0 (M+H+).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux
  3. customThe organic phase was separated
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. additionThe resultant solid was treated with EtOAc (5 mL)
  8. customsonicated for 5 min
  9. filtrationthen filtered free of solids
  10. customevaporated to a small volume
  11. customthe solution purified by column chromatography

Sources & evidence

ORD record
ord-7415d5b5de9847c1aa7b6ba9cfb071b9
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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