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 1485323노트

반응식

HRID 1485323 반응식
[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]

참가 물질

7

반응물 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

생성물 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)methanone수율 2.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-5835ae17c60848a08201b91958dbcc3e
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422267B2

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