Ammonia → (S)-N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

HRID 1485322Notes

Reaction equation

HRID 1485322 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.[NH3:34]>O1CCOCC1>[NH2:34][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

Participants

4

Reactant 2

HCID 222AmmoniaHCID 76072890(S)-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

Product 1

HCID 86723665(S)-N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)—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 (250 mg, 0.55 mmol) in 1,4-dioxane (5 mL) was added aqueous ammonia (5 mL) and the reaction mixture was allowed to reflux in steel bomb at 130° C. for 18 h. The reaction mixture was concentrated under vacuum to obtain an oily crude product which was purified by reverse phase HPLC to afford 8 mg of (S)—N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide. 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 1.20 (d, 6H), 2.00-2.20 (m, 4H), 2.75-2.95 (m, 5H), 3.50-3.90 (m, 4H), 4.90-4.98 (m, 1H), 6.40 (s, 1H), 6.50 (d, 1H), 7.40 (s, 1H), 7.90 (s, 1H). The other enantiomer is prepared using the chiral (R) starting material.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customto obtain an oily crude product which
  3. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-204eb080c785498a861a23fbd13d9019
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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