Piperidine → (R)-(1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidin-2-yl)(piperidin-1-yl)methanone

HRID 1485323Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1485323
[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:26][CH2:25][CH2:24][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH:17]3[C:21](O)=[O:22])[N:15]=2)[CH:5]=1)([CH3:3])[CH3:2].[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:26][CH2:25][CH2:24][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@@H:17]3[C:21]([N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:22])[N:15]=2)[CH:5]=1)([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867236291-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid

Produkt 1

HCID 86723666(R)-(1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidin-2-yl)(piperidin-1-yl)methanoneAusbeute 2,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid (400 mg, 1.12 mmol), piperidine (143 mg, 1.68 mmol), HATU (512 g, 1.34 mmol) and DIPEA (230 mg, 1.79 mmol) in DMF (4 mL) was allowed to stir at RT overnight. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layer was washed with water (8×25 mL) and dried over anhydrous sodium sulfate. Removal of EtOAc gave an oily residue which 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)pyrrolidin-2-yl)(piperidin-1-yl)methanone, and its enantiomer. 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 1.30 (d, 6H), 1.40-1.90 (m, 6H), 1.92-2.12 (m, 5H), 2.30-2.42 (m, 1H), 2.65-2.81 (m, 4H), 2.90-3.01 (m, 1H), 3.40-3.90 (m, 6H), 5.00-5.08 (m, 1H), 6.00 (brs, 1H).

Aufarbeitung

  1. extractionextracted with EtOAc (2×50 mL)
  2. washThe combined organic layer was washed with water (8×25 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customRemoval of EtOAc
  5. customgave an oily residue which
  6. customwas purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-5835ae17c60848a08201b91958dbcc3e
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09422267B2

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