1,2-Dichloroethane → HCID 86637008, compound

HRID 1366619Notes

Reaction equation

HRID 1366619 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]([CH3:14])([CH3:13])[CH2:11][CH:10]([N:15]([CH3:17])[CH3:16])[CH2:9]2)[C:5]([F:18])=[C:4]([NH:19][NH2:20])[N:3]=1.[CH:21]1([CH2:26][C@H:27]([CH2:31][N:32]([CH:41]=[O:42])[O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:28](O)=[O:29])[CH2:25][CH2:24][CH2:23][CH2:22]1.CN1CCOCC1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C.CCOCC>[Cl:1][C:2]1[N:3]=[C:4]([NH:19][NH:20][C:28](=[O:29])[C@H:27]([CH2:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)[CH2:31][N:32]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:41]=[O:42])[C:5]([F:18])=[C:6]([N:8]2[CH2:9][CH:10]([N:15]([CH3:16])[CH3:17])[CH2:11][C:12]2([CH3:14])[CH3:13])[N:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 86637006HCID 86637006, compound

Product 1

HCID 86637008HCID 86637008, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-N,N,5,5-tetramethyl-3-pyrrolidinamine (1.0502 g, 3.469 mmol) in DMF (16 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (1.0075 g, 3.299 mmol), N-methylmorpholine (1.8 mL, 16.37 mmol), 1-hydroxy-7-azabenzotriazole (0.540 g, 3.968 mmol), and EDC (0.760 g, 3.964 mmol). The solution was stirred overnight and then diluted with Et2O (100 mL). The mixture was washed with water (3×50 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (50 mL). This organic phase was washed with a fresh portion of water (25 mL), and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in DCM (150 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to provide crude [(2R)-3-(2-{2-chloro-6-[4-(dimethylamino)-2,2-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (1.6539 g, 85% crude yield) as a dark red foam. LCMS: (M+H)+: 590.2.

Workup

  1. washThe mixture was washed with water (3×50 mL)
  2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (50 mL)
  3. washThis organic phase was washed with a fresh portion of water (25 mL)
  4. dry with materialthe combined organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in DCM (150 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ad153510d154b4b9c9934c51736b937
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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