1,2-Dichloroethane → HCID 87210495, compound

HRID 1366545Notes

Reaction equation

HRID 1366545 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][C:11]([CH3:14])([CH3:13])[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])[C:11]([CH3:14])([CH3:13])[CH2:12]2)[N:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 87210185HCID 87210185, compound

Product 1

HCID 87210495HCID 87210495, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of racemic 1-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-N,N,4,4-tetramethyl-3-pyrrolidinamine (7.37 g, 24.34 mmol, prepared according to the procedures of Example 133) in DMF (77 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (7.08 g, 23.18 mmol), N-methylmorpholine (12.75 mL, 116.0 mmol), 1-hydroxy-7-azabenzotriazole (3.79 g, 27.85 mmol), and EDC (5.33 g, 27.80 mmol). The solution was stirred overnight and was then diluted with Et2O (100 mL) and washed with water (3×100 mL). The combined aqueous phase was extracted with a fresh portion of Et2O (100 mL), and this organic phase was washed with a fresh portion of water (50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was diluted with EtOAc (200 mL), and the resulting solution was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford crude [(2R)-3-(2-{2-chloro-6-[4-(dimethylamino)-3,3-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (12.52 g, 92% yield, mixture of diastereomers). LCMS: (M+H)+: 590.2.

Workup

  1. washwashed with water (3×100 mL)
  2. extractionThe combined aqueous phase was extracted with a fresh portion of Et2O (100 mL)
  3. washthis organic phase was washed with a fresh portion of water (50 mL)
  4. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted with EtOAc (200 mL)
  8. dry with materialthe resulting solution was dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1c64d3c640b94ab59d381b16d99615d6
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…