Diisopropylethylamine → Phenylmethyl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-({[4-(2-pyridinyl)-2-pyrimidinyl]amino}carbonyl)-1-pyrazolidinecarboxylate

HRID 1396963Notes

Reaction equation

HRID 1396963 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:28][N:29]([CH:37]=[O:38])[O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[C:8]([N:10]2[C@H:14]([C:15]([OH:17])=O)[CH2:13][CH2:12][N:11]2[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.CCN(C(C)C)C(C)C.[N:60]1[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=1[C:66]1[CH:71]=[CH:70][N:69]=[C:68]([NH2:72])[N:67]=1>C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH:1]1([CH2:6][C@H:7]([CH2:28][N:29]([CH:37]=[O:38])[O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[C:8]([N:10]2[C@H:14]([C:15]([NH:72][C:68]3[N:67]=[C:66]([C:61]4[CH:62]=[CH:63][CH:64]=[CH:65][N:60]=4)[CH:71]=[CH:70][N:69]=3)=[O:17])[CH2:13][CH2:12][N:11]2[C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:19])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 27645994-(Pyridin-2-yl)pyrimidin-2-amineHCID 131732108(3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Product 1

HCID 131732107Phenylmethyl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-({[4-(2-pyridinyl)-2-pyrimidinyl]amino}carbonyl)-1-pyrazolidinecarboxylateYield 39%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (800 mg, 1.5 mmol) in THF (10 mL) under N2 was added 2,4,6-trichlorobenzoyl chloride (477 mg, 2 mmol) and DIPEA (1.3 mL, 7.5 mmol). The mixture was stirred at rt for 2 h. THF was removed under vacuum and toluene (10 mL) was added. To this mixture was added 4-(2-pyridinyl)-2-pyrimidinamine (337 mg, 2 mmol) and DMAP (37 mg, 0.3 mmol). After being stirred at rt overnight, the mixture was diluted with EtOAc (50 mL) and washed with 5% citric acid and sat. NaHCO3. The organic solution was dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography to provide the title compound (400 mg, 39%).

Workup

  1. customTHF was removed under vacuum and toluene (10 mL)
  2. additionwas added
  3. stirringAfter being stirred at rt overnight
  4. washwashed with 5% citric acid and sat. NaHCO3
  5. dry with materialThe organic solution was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-0ec703d6ae49482d927ca1db20eced39
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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