Potassium Iodide → (R)-tert-butyl 1-(3-(4-((2-amino-4-(mesitylsulfonyloxy)-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

HRID 2207087Notes

Reaction equation

HRID 2207087 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH3:21][C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[C:23]=1[S:30]([O:33][C:34]1[C:39]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][CH2:50]OS(C)(=O)=O)=[CH:43][C:42]=2[O:56][CH3:57])=[C:38]([CH3:58])[N:37]=[C:36]([NH2:59])[N:35]=1)(=[O:32])=[O:31]>CC#N.O>[NH2:59][C:36]1[N:35]=[C:34]([O:33][S:30]([C:23]2[C:24]([CH3:29])=[CH:25][C:26]([CH3:28])=[CH:27][C:22]=2[CH3:21])(=[O:32])=[O:31])[C:39]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][CH2:50][N:1]3[CH2:5][CH2:4][CH2:3][C@@H:2]3[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:43][C:42]=2[O:56][CH3:57])=[C:38]([CH3:58])[N:37]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 6931635H-D-Pro-otbuHCID 1179926812-Amino-5-(2-methoxy-4-(3-(methylsulfonyloxy)propoxy)benzyl)-6-methylpyrimidin-4-yl 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 117992770(R)-tert-butyl 1-(3-(4-((2-amino-4-(mesitylsulfonyloxy)-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

(R)-tert-butyl pyrrolidine-2-carboxylate (485 mg) was added to the mixture of potassium carbonate (393 mg), potassium iodide (31 mg) and the crude product from step (viii) in CH3CN (20 mL). After the mixture was stirred at 70° C. for 16 h, the reaction mixture was cooled to RT, diluted with water and extracted with EtOAc. The combined organic layer was washed with water and brine, dried and concentrated under reduced pressure. The residue was purified by flash column chromatography on amino silica gel to afford the sub-title compound (975 mg) as a white amorphous solid; 1H NMR (300 MHz, CDCl3); 6.92 (2H, s), 6.67 (1H, d), 6.39 (1H, d), 6.30 (1H, dd), 4.64 (2H, br s), 4.03-3.90 (2H, m), 3.76 (3H, s), 3.73 (2H, s), 3.20-3.00 (2H, m), 2.96-2.80 (1H, m), 2.66-2.50 (1H, m), 2.57 (6H, s), 2.46-2.30 (1H, m), 2.28 (3H, s), 2.22 (3H, s), 2.21-1.74 (6H, m), 1.43 (9H, s); LC-MS: m/z 655.

Workup

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

Sources & evidence

ORD record
ord-ed3a1177b5164bf990635f31a9748922
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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