Sodium methanethiolate → HCID 86723668, compound

HRID 1485325Notes

Reaction equation

HRID 1485325 reaction equation
F[C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]2[N:17]=[C:18]([NH:25][C:26]3[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[NH:28][N:27]=3)[C:19]3[CH2:24][CH2:23][CH2:22][C:20]=3[N:21]=2)=[O:10])=[CH:4][CH:3]=1.[CH3:34][S-:35].[Na+]>C(O)C>[CH:31]([C:29]1[NH:28][N:27]=[C:26]([NH:25][C:18]2[C:19]3[CH2:24][CH2:23][CH2:22][C:20]=3[N:21]=[C:16]([N:12]3[CH2:13][CH2:14][CH2:15][C@@H:11]3[C:9]([NH:8][C:5]3[CH:6]=[N:7][C:2]([S:35][CH3:34])=[CH:3][CH:4]=3)=[O:10])[N:17]=2)[CH:30]=1)([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 4378561Sodium methanethiolateHCID 86723669HCID 86723669, compound

Product 1

HCID 86723668HCID 86723668, compoundYield 4.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of (R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide (200 mg, 0.44 mmol) and sodium thiomethoxide (100 mg, 1.42 mmol) in ethanol (2 mL) was heated at 100° C. in a microwave for 1 h. The solvent was removed under reduced pressure and the residue was diluted with EtOAc (50 mL). The solution was washed with saturated sodium bicarbonate solution (20 mL) followed by brine (20 mL), and dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure gave an oily residue that was purified by reverse phase HPLC followed by chiral HPLC to afford 10 mg of (R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-(methylthio)pyridin-3-yl)pyrrolidine-2-carboxamide. 1HNMR (400 MHz, CDCl3) δ (ppm): 1.18-1.32 (m, 6H), 1.90-2.20 (m, 5H), 2.51 (s, 3H), 2.60-2.77 (m, 3H), 2.84-2.98 (m, 3H), 3.60-3.79 (m, 2H), 4.78 (d, 1H), 6.40 (s, 1H), 6.70 (s, 1H), 7.08 (d, 1H), 7.98 (brs, 1H), 8.20 (s, 1H). The other enantiomer is prepared using the (S) starting material.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with EtOAc (50 mL)
  3. washThe solution was washed with saturated sodium bicarbonate solution (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customRemoval of EtOAc under reduced pressure
  6. customgave an oily residue that
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5f96d74a3ec84badabbbade0fddc68ef
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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