Hexamethylphosphoramide → HCID 57955616, compound

HRID 914174Notes

Reaction equation

HRID 914174 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9](=[CH:14][CH3:15])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.C([N-]C(C)C)(C)C.[Li+].CN(C)P(N(C)C)(N(C)C)=O.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:51])(=O)=O)=CC=1>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:51])([CH:14]=[CH2:15])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1

Participants

7

Reactant 4

HCID 12679HexamethylphosphoramideHCID 588007N-FluorobenzenesulfonimideHCID 2724682Lithium diisopropylamideHCID 76674569HCID 76674569, compound

Product 1

HCID 57955616HCID 57955616, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

2-Chloro-9-cyclopentyl-7-ethylidene-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (1.01 g, 3.30 mmol) in dry tetrahydrofuran (10 mL) was added to 1:1 molar 2 M lithium diisopropyl amide in tetrahydrofuran and hexamethyl phosphoramide (HMPA) (3.96 mmol each) in tetrahydrofuran (5 mL) at −78° C. After 20 minutes, N-fluorobenzene sulfonimide (2.46 mmol) was added dropwise to it. Continued the reaction at −78° C. for 30 minutes, and then elevated the temperature to 0° C. for 30 minutes. After disappearing the starting material, cooled the reaction flask to −78° C., then quenched with sat. ammonium chloride solution (6 mL). At room temperature, the resultant reaction mixture was taken into ethyl acetate (70 mL), washed with ammonium chloride solution and finally with water, dried over sodium sulphate and evaporated. Purified the product using column chromatography with hexane:ethyl acetate mixtures to give the product. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.53-2.10 (m, 8H) 3.38 (s, 3H) 3.63-3.88 (m, 1H) 4.12 (m, 1H) 4.96 (quin, J=8.59 Hz, 1H) 5.41 (d, J=11.12 Hz, 1H) 5.49 (dd, J=17.18, 2.02 Hz, 1H) 6.02 (ddd, J=17.37, 14.72, 10.86 Hz, 1H) 7.97 (s, 1H). [M+H] calculated for C15H18ClFN4O, 325. found 325.

Workup

  1. customat −78° C
  2. customContinued the reaction at −78° C. for 30 minutes
  3. customto 0° C.
  4. customfor 30 minutes
  5. customquenched with sat. ammonium chloride solution (6 mL)
  6. customAt room temperature, the resultant reaction mixture
  7. washwashed with ammonium chloride solution and finally with water
  8. dry with materialdried over sodium sulphate
  9. customevaporated
  10. customPurified the product
  11. customethyl acetate mixtures to give the product

Sources & evidence

ORD record
ord-38782f1eb9814a8781eb985a0af58743
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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