1,2-Dichloroethane → HCID 86636953, compound

HRID 1366477Notes

Reaction equation

HRID 1366477 reaction equation
[CH3:1][C@@H:2]1[CH2:7][N:6]([CH3:8])[CH2:5][CH2:4][N:3]1[C:9]1[C:14]([F:15])=[C:13]([NH:16][NH2:17])[N:12]=[C:11]([CH3:18])[N:10]=1.C(N(C(C)C)CC)(C)C.[CH:28]1([CH2:33][C@H:34]([CH2:38][N:39]([CH:48]=[O:49])[O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:35](O)=[O:36])[CH2:32][CH2:31][CH2:30][CH2:29]1.C(O)(C)C.CN1CCOCC1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CN(C)C=O.CCOCC>[CH:28]1([CH2:33][C@@H:34]([C:35]([NH:17][NH:16][C:13]2[C:14]([F:15])=[C:9]([N:3]3[CH2:4][CH2:5][N:6]([CH3:8])[CH2:7][C@H:2]3[CH3:1])[N:10]=[C:11]([CH3:18])[N:12]=2)=[O:36])[CH2:38][N:39]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:48]=[O:49])[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 3776IsopropanolHCID 79724-MethylmorpholineHCID 181649HOAtHCID 66936055HCID 66936055, compoundHCID 86636954HCID 86636954, compound

Product 1

HCID 86636953HCID 86636953, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[(2R)-2,4-dimethyl-1-piperazinyl]-5-fluoro-6-hydrazino-2-methylpyrimidine (8.04 g, assumed 31.4 mmol) in N,N-dimethylformamide (125 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid diisopropylethylamine salt, isopropanol solvate (15.48 g, 31.3 mmol), N-methylmorpholine (17.21 mL, 156 mmol), 1-hydroxy-7-azabenzotriazole (5.11 g, 37.6 mmol), and EDC (7.20 g, 37.6 mmol). The solution was stirred overnight, and then diluted with Et2O (150 mL) and washed with water (2×100 mL). The combined aqueous phase was extracted with a fresh portion of Et2O (150 mL), and this organic phase was washed with water (75 mL). The total combined aqueous phase was extracted with another fresh portion of Et2O (150 mL), and this organic phase was washed with water (75 mL). The combined organic phase was diluted with DCM (100 mL), and dried over anhydrous Na2SO4. The mixture was filtered and concentrated in vacuo to give crude [(2R)-2-(cyclopentylmethyl)-3-(2-{6-[(2R)-2,4-dimethyl-1-piperazinyl]-5-fluoro-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (15.60 g, 28.8 mmol, 92% yield) as a light brown foam. LCMS: (M+H)+: 541.7.

Workup

  1. washwashed with water (2×100 mL)
  2. extractionThe combined aqueous phase was extracted with a fresh portion of Et2O (150 mL)
  3. washthis organic phase was washed with water (75 mL)
  4. extractionThe total combined aqueous phase was extracted with another fresh portion of Et2O (150 mL)
  5. washthis organic phase was washed with water (75 mL)
  6. additionThe combined organic phase was diluted with DCM (100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8fd7eb27385842c281d48f96ee4a4e38
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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