Sodium Iodide → HCID 178508235, compound

HRID 335966Notes

Reaction equation

HRID 335966 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[O:14][C:15]4[C:20]([C@@:21]5([CH2:25][O:24][C:23]([NH2:26])=[N:22]5)[C:10]=3[CH:9]=2)=[CH:19][C:18]([C:27]2[C:28]([O:33]C)=[N:29][CH:30]=[CH:31][CH:32]=2)=[CH:17][CH:16]=4)[CH:5]=[CH:4][N:3]=1.COC1C(B(O)O)=CC=CN=1.FC1C=C(B(O)O)C=CN=1.[I-].[Na+].Cl[Si](C)(C)C>C(#N)C>[NH2:26][C:23]1[O:24][CH2:25][C@:21]2([C:10]3[CH:9]=[C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([F:1])[CH:7]=4)[N:13]=[CH:12][C:11]=3[O:14][C:15]3[C:20]2=[CH:19][C:18]([C:27]2[C:28]([OH:33])=[N:29][CH:30]=[CH:31][CH:32]=2)=[CH:17][CH:16]=3)[N:22]=1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 27833962-Fluoropyridine-4-boronic acidHCID 58466310HCID 58466310, compound

Product 1

HCID 178508235HCID 178508235, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of (S)-3-(2-fluoropyridin-4-yl)-7-(2-methoxypyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (0.075 g, 0.17 mmol, prepared as described in BB41 and AA1 using 2-methoxypyridin-3-ylboronic acid and 2-fluoropyridin-4-ylboronic acid) and sodium iodide, anhydrous (0.077 g, 0.51 mmol) in acetonitrile (6.0 mL) was treated chlorotrimethylsilane (0.070 mL, 0.55 mmol) and the resulting mixture was stirred at room temperature for 16 h. The reaction was concentrated to dryness on the rotary evaporator, the resulting residue was taken up in dichloromethane (25 mL), water (15 mL), and formation of insoluble solids was observed. The solids were collected by filtration. The solid was dissolved in DMSO (1.5 mL) and loaded on the AGILENT MASS-TRIGGERRED HPLC system for purification using a MeCN/Water/0.1% TFA gradient and PHENOMENEX Gemini Axia-5 C-18 column (150×30 mm). The solvent was removed from the pure fractions in the GENEVAC and the resulting product was dissolved in methanol (1.5 mL) and neutralized by passing the solution through a Polymer Lab-HCO3 Macroporous resin cartridge (0.36 mmol loading; 500 mgs), and the filtrate was concentrated under high vacuum to yield the product (S)-3-(2′-amino-3-(2-fluoropyridin-4-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazole]-7-yl)pyridin-2-ol as an amorphous off-white solid [MS: m/z=442.1 (M+H)].

Workup

  1. customprepared
  2. concentrationThe reaction was concentrated to dryness on the rotary evaporator
  3. filtrationThe solids were collected by filtration
  4. dissolutionThe solid was dissolved in DMSO (1.5 mL)
  5. customloaded on the AGILENT MASS-TRIGGERRED HPLC system for purification
  6. customThe solvent was removed from the pure fractions in the GENEVAC
  7. dissolutionthe resulting product was dissolved in methanol (1.5 mL)
  8. concentrationthe filtrate was concentrated under high vacuum

Sources & evidence

ORD record
ord-ecedddd5c4bb4802934aa6f5771518a1
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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