Hydrochloric Acid → HCID 71470358, compound

HRID 1424556Notes

Reaction equation

HRID 1424556 reaction equation
[F:1][C:2]1[C:7]([F:8])=[C:6]([C:9]#[C:10][C:11]2[C:17]([C:18]#[C:19][C:20]3[C:25]([F:26])=[C:24]([F:27])[N:23]=[C:22]([F:28])[C:21]=3[F:29])=[CH:16][CH:15]=[CH:14][C:12]=2[NH2:13])[C:5]([F:30])=[C:4]([F:31])[N:3]=1.P(Cl)(Cl)([Cl:34])=O.[NH2:37][C@H:38]([C:44](O)=[O:45])[CH2:39][CH2:40][CH2:41][CH2:42][NH2:43].[ClH:47]>N1C=CC=CC=1.C1COCC1>[ClH:34].[ClH:47].[NH2:37][CH:38]([CH2:39][CH2:40][CH2:41][CH2:42][NH2:43])[C:44]([NH:13][C:12]1[CH:14]=[CH:15][CH:16]=[C:17]([C:18]#[C:19][C:20]2[C:25]([F:26])=[C:24]([F:27])[N:23]=[C:22]([F:28])[C:21]=2[F:29])[C:11]=1[C:10]#[C:9][C:6]1[C:5]([F:30])=[C:4]([F:31])[N:3]=[C:2]([F:1])[C:7]=1[F:8])=[O:45]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5962L-LysineHCID 24813Phosphorus oxychlorideHCID 86673525HCID 86673525, compound

Product 1

HCID 71470358HCID 71470358, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

L-Boc-Lys(Boc)-OH (0.31 g, 0.91 mmol) and compound (19) (0.20 g, 0.46 mmol) were dissolved in 2 mL of pyridine. The solution was cooled to −25° C. and phosphorus oxychloride (0.14 g, 0.91 mmol) was added dropwise with vigorous stirring. After stirring for 30 min. at -25° C., the reaction mixture was stirred at room temperature for 10 h. The reaction mixture was quenched with ice/water and extracted with EtOAc. The organic layer was washed with sat. NaHSO4 three times, dried with Na2SO4 and was concentrated in vacuo. The crude product was subjected to chromatography with CH3CN:CH2Cl2=1:40 and the Boc-protected product was obtained in 26% yield. Into the solution of the Boc-protected lysine conjugate (85 mg, 0.11 mmol) in THF was gaseous HCl bubbled at 0° C. for 1 hr and the solution was stirred for 1 hour at room temperature. The solvent was evaporated and the desired product (46 mg, 65%) was purified by recrystallization with EtOH: 1H-NMR (300 MHz, CD3OD) δ 8.07 (dd, J=6.3 Hz, J=3.0 Hz, 1H), 7.69 (m, 2H), 4.26 (dd, J=7.5 Hz, J=5.4 Hz, 1H), 2.98 (t, J=H7.2 Hz, 2H), 2.01-2.21 (m, 2H), 1.75-1.81 (m, 2H), 1.60-1.75 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 10 h
  2. customThe reaction mixture was quenched with ice/water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with sat. NaHSO4 three times
  5. dry with materialdried with Na2SO4
  6. concentrationwas concentrated in vacuo
  7. customwas obtained in 26% yield
  8. custombubbled at 0° C. for 1 hr
  9. stirringthe solution was stirred for 1 hour at room temperature
  10. customThe solvent was evaporated
  11. customthe desired product (46 mg, 65%) was purified by recrystallization with EtOH

Sources & evidence

ORD record
ord-0224d8399cf748bc99b0d51d23596dd7
Source dataset
uspto-grants-2015_01
Patent number
US08927728B2

Reaction notes

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