1,2-Dichloroethane → [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide

HRID 1366678노트

반응식

HRID 1366678 반응식
[F:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][C@@H:12]2[CH3:17])=[N:4][C:5]([CH3:10])=[N:6][C:7]=1[NH:8][NH2:9].[CH:18](O)([CH3:20])[CH3:19].CN1C[CH2:27][O:26]CC1.[OH:29][N:30]1[C:34]2N=[CH:36][CH:37]=[CH:38][C:33]=2N=N1.C(Cl)CCl.CN([CH:46]=[O:47])C>>[CH:37]1([CH2:38][C@@H:33]([C:27]([NH:9][NH:8][C:7]2[C:2]([F:1])=[C:3]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][C@@H:12]3[CH3:17])[N:4]=[C:5]([CH3:10])[N:6]=2)=[O:26])[CH2:34][N:30]([OH:29])[CH:46]=[O:47])[CH2:36][CH2:20][CH2:18][CH2:19]1

참가 물질

7

반응물 6

HCID 111,2-DichloroethaneHCID 3776IsopropanolHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 181649HOAtHCID 66936366(3S)-4-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-3-methylmorpholine

생성물 1

HCID 58000539[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide수율 80%

실험 절차

To a solution of (3S)-4-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-3-methylmorpholine (0.2123 g, 0.880 mmol) in DMF (4 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid, N,N-diisopropylethylamine salt, isopropanol solvate (327.1 mg, 0.661 mmol), N-methylmorpholine (0.290 ml, 2.64 mmol), 1-hydroxy-7-azabenzotriazole (0.108 g, 0.794 mmol), and EDC (0.152 g, 0.793 mmol). The solution was stirred overnight, and then purified directly by Gilson RPLC. To a solution of the residue in MeOH (7 mL) was added 10% Pd/C (50% water, 88 mg). The mixture was hydrogenated under balloon pressure for 1 h, and then filtered through a PTFE membrane. The resulting solution was concentrated in vacuo, dissolved in EtOAc, and concentrated in vacuo. The solid was collected by vacuum filtration and washed with hexanes to give [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide (0.2326 g, 80% yield) as a white solid. LCMS: (M+H)+: 439.2.

후처리

  1. custompurified directly by Gilson RPLC
  2. additionTo a solution of the residue in MeOH (7 mL) was added 10% Pd/C (50% water, 88 mg)
  3. waitThe mixture was hydrogenated under balloon pressure for 1 h
  4. filtrationfiltered through a PTFE membrane
  5. concentrationThe resulting solution was concentrated in vacuo
  6. dissolutiondissolved in EtOAc
  7. concentrationconcentrated in vacuo
  8. filtrationThe solid was collected by vacuum filtration
  9. washwashed with hexanes

출처 및 근거

ORD 기록
ord-ede382fb3b02453dbf7a0a24929cf59c
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893056B2

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