Potassium Iodide → (S)-methyl 1-(3-(4-((4-((S)-1-acetoxyhexan-3-ylamino)-2-amino-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

HRID 2207095Notes

Reaction equation

HRID 2207095 reaction equation
Cl.[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][NH:7]1)=[O:5].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[C:19]([O:22][CH2:23][CH2:24][C@@H:25]([NH:29][C:30]1[C:35]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH2:46]OS(C)(=O)=O)=[CH:39][C:38]=2[O:52][CH3:53])=[C:34]([CH3:54])[N:33]=[C:32]([NH2:55])[N:31]=1)[CH2:26][CH2:27][CH3:28])(=[O:21])[CH3:20]>C(#N)C.O.C(OC([O-])=O)(O)=O.[Na+]>[C:19]([O:22][CH2:23][CH2:24][C@@H:25]([NH:29][C:30]1[C:35]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH2:46][N:7]3[CH2:8][CH2:9][CH2:10][C@H:6]3[C:4]([O:3][CH3:2])=[O:5])=[CH:39][C:38]=2[O:52][CH3:53])=[C:34]([CH3:54])[N:33]=[C:32]([NH2:55])[N:31]=1)[CH2:26][CH2:27][CH3:28])(=[O:21])[CH3:20]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 2733200methyl L-prolinate hydrochlorideHCID 89906963(S)-3-(2-amino-5-(2-methoxy-4-(3-(methylsulfonyloxy)propoxy)benzyl)-6-methylpyrimidin-4-ylamino)hexyl acetate

Product 1

HCID 117992586(S)-methyl 1-(3-(4-((4-((S)-1-acetoxyhexan-3-ylamino)-2-amino-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylateYield 75.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 88008498Sodium hydrogen dicarbonateSolvent

Conditions

Temperature
70 °C

Procedure

(S)-methylpyrrolidine-2-carboxylate hydrochloride (44 mg) was added to the mixture of potassium carbonate (74 mg), potassium iodide (3 mg) and the crude product (75 mg) from step (v) in acetonitrile (2 mL). After the mixture was stirred at 70° C. for 16 h, the reaction mixture was cooled to RT, diluted with water and sat. sodium hydrogen dicarbonate and extracted with EtOAc. The combined organic layer was dried and concentrated under reduced pressure. The residue was purified by flash column chromatography on amino silica gel to afford the sub-title compound (60 mg) as a colourless oil; 1H NMR (CDCl3); 6.80 (1H, d), 6.44 (1H, d), 6.37 (1H, dd), 4.85 (2H, br s), 4.24-4.15 (1H, m), 4.00-3.87 (4H, m), 3.85 (3H, s), 3.67 (3H, s), 3.57 (2H, s), 3.22-3.14 (2H, m), 2.89-2.78 (1H, m), 2.61-2.50 (1H, m), 2.42-2.30 (1H, m), 2.34 (3H, s), 2.16-2.05 (1H, s), 1.97 (3H, s), 1.97-1.70 (6H, m), 1.63-1.49 (1H, m), 1.46-1.32 (1H, m), 1.29-1.15 (1H, m), 1.12-0.98 (2H, m), 0.77 (3H, t); LC-MS: m/z 572.

Workup

  1. temperaturethe reaction mixture was cooled to RT
  2. extractionextracted with EtOAc
  3. customThe combined organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on amino silica gel

Sources & evidence

ORD record
ord-fe1bea2c871d4aaebdb8d6a5a1032af2
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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