Sodium Iodide → HCID 89955667, compound

HRID 1526787Notes

Reaction equation

HRID 1526787 reaction equation
OC(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[C:11]([C@@H:24]([NH:29][C:30](=[O:50])[CH2:31][NH:32][C:33](=[O:49])[C:34]2[CH:39]=[C:38]([NH:40][C:41]3[NH:42][CH2:43][CH:44]([OH:47])[CH2:45][N:46]=3)[CH:37]=[C:36]([OH:48])[CH:35]=2)[CH2:25][C:26]([OH:28])=[O:27])[CH:12]=[C:13]([C:15]2([CH2:21][O:22]C)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1.C1OCCOCCOCCOCCOC1.[I-].[Na+].C(=O)=O.CC#N.B(Br)(Br)Br>ClCCl>[Cl:8][C:9]1[CH:10]=[C:11]([C@@H:24]([NH:29][C:30](=[O:50])[CH2:31][NH:32][C:33](=[O:49])[C:34]2[CH:39]=[C:38]([NH:40][C:41]3[NH:46][CH2:45][CH:44]([OH:47])[CH2:43][N:42]=3)[CH:37]=[C:36]([OH:48])[CH:35]=2)[CH2:25][C:26]([OH:28])=[O:27])[CH:12]=[C:13]([C:15]2([CH2:21][OH:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 25134Boron tribromideHCID 3633615-Crown-5HCID 86587134Acetonitrile dry iceHCID 131733188HCID 131733188, compound

Product 1

HCID 89955667HCID 89955667, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-30 °C

Procedure

To a solution of (3S)-3-(3-chloro-5-(4-(Methoxymethyl)tetrahydro-2H-pyran-4-yl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid TFA salt (Example 16) (85.5 mg, 0.117 mmol) in anhydrous dichloromethane (2.0 mL) was added a solution of 15-crown-5 (155.0 mg, 0.702 mmol) saturated with sodium iodide in dichloromethane (6.0 mL) at room temperature and the reaction mixture was cooled to −30° C. (dry-ice/CH3CN) and a 1.0 M BBr3 solution in dichloromethane (350 μL, 0.35 mmol) was added and the reaction mixture stirred at −30° C. for 2 h to give an orange suspension. After 2 hr the reaction mixture was allowed to warm slowly to room temperature and stirred at room temperature overnight to give an orange-cream suspension. The suspension was filtered, washed with dichloromethane (2×10 mL) and dried in vacuo to give a yellow-cream solid. The crude product was purified by reverse-phase HPLC with a gradient 10-50% CH3CN in water containing 0.05% TFA to give the desired product (Example 17), after lyophilization, as a colorless lyophilized solid (64.5 mg). LC/MS analysis of the product shows the desired product's mass: m/z 604 (35ClM+H), m/z 606 (37ClM+H), m/z 626 (35ClM+Na), and m/z 628 (37ClM+Na), Calcd for C28H34ClN5O8:604.05.

Workup

  1. customto give an orange suspension
  2. waitAfter 2 hr the reaction mixture was allowed
  3. temperatureto warm slowly to room temperature
  4. stirringstirred at room temperature overnight
  5. customto give an orange-cream suspension
  6. filtrationThe suspension was filtered
  7. washwashed with dichloromethane (2×10 mL)
  8. customdried in vacuo
  9. customto give a yellow-cream solid
  10. customThe crude product was purified by reverse-phase HPLC with a gradient 10-50% CH3CN in water containing 0.05% TFA

Sources & evidence

ORD record
ord-b50f91e6633f4ad2a4d1df011e3a45e2
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

Loading…