Ethanol → HCID 86723671, compound

HRID 1485327Notes

Reaction equation

HRID 1485327 reaction equation
F[C:2]1[C:7]([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:6][CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:40]([OH:42])[CH3:41]>>[CH2:40]([O:42][C:2]1[C:7]([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:6][CH:5]=[CH:4][N:3]=1)[CH3:41]

Participants

4

Reactant 3

HCID 702EthanolHCID 10796Cesium carbonateHCID 86723672HCID 86723672, compound

Product 1

HCID 86723671HCID 86723671, compound

Conditions

Temperature
80 °C

Procedure

To a suspension of (S)—N-(2-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide (25 mg, 0.053 mmol) in ethanol (1 mL) was added Cs2CO3 (26 mg, 0.080 mmol) and the reaction mixture was allowed to stir at 80° C. for 12 h. The reaction mixture was concentrated, diluted with water (20 mL) and extracted with EtOAc (2×20 mL). The combined organic layer was dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure gave an oily residue that was purified by reverse phase HPLC to afford 8 mg of (S)—N-(2-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide as the TFA salt. 1HNMR (400 MHz, CD3OD) δ (ppm): 1.00-1.17 (m, 6H), 1.27 (t, 3H), 2.08-2.30 (m, 4H), 2.36-2.42 (m, 2H), 2.70-2.90 (m, 3H), 2.92-3.03 (m, 2H), 3.60-3.70 (m, 1H), 3.78-3.88 (m, 1H), 4.37 (q, 2H), 4.85-4.95 (m, 1H), 6.24 (s, 1H), 6.82-6.92 (m, 1H), 7.78-7.93 (m, 1H), 8.10-8.18 (m, 1H). The other enantiomer is prepared using the (R) chiral starting material.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water (20 mL)
  3. extractionextracted with EtOAc (2×20 mL)
  4. dry with materialThe combined organic layer was dried 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-7d7cd332442e47e5b875b5414f49fe63
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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