1,2-Dichloroethane → HCID 86640591, compound

HRID 1893212Notes

Reaction equation

HRID 1893212 reaction equation
[CH3:1][S:2]([O:5][C:6]1[C:21](=[O:22])[N:10]2[CH2:11][C@@H:12]([O:19][CH3:20])[CH2:13][CH2:14][C@@H:15]([NH:16][CH2:17][CH3:18])[C:9]2=[N:8][C:7]=1[C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)=[O:24])(=[O:4])=[O:3].[CH3:34][N:35]([CH3:41])[C:36](=[O:40])[C:37](O)=[O:38].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CS(Cl)(=O)=O>C(Cl)Cl.O.C(#N)C>[CH3:1][S:2]([O:5][C:6]1[C:21](=[O:22])[N:10]2[CH2:11][C@@H:12]([O:19][CH3:20])[CH2:13][CH2:14][C@@H:15]([N:16]([C:37](=[O:38])[C:36]([N:35]([CH3:41])[CH3:34])=[O:40])[CH2:17][CH3:18])[C:9]2=[N:8][C:7]=1[C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)=[O:24])(=[O:3])=[O:4]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 31297Methanesulfonyl chlorideHCID 181649HOAtHCID 2760995N,N-Dimethyloxamic acidHCID 59271869HCID 59271869, compound

Product 1

HCID 86640591HCID 86640591, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the (7S,10R)-10-(ethylamino)-2-{[(4-fluorobenzyl)amino]carbonyl}-7-methoxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-3-yl methanesulfonate (4.8 g, 9.99 mmol) in DCM (100 mL) at room temperature was added TEA (8.35 mL, 59.9 mmol), N,N-dimethyloxamic acid (2.34 g, 19.98 mmol), EDC (5.74 g, 30 mmol), and HOAt (4.62 g, 30 mmol). The resulting mixture was stirred at room temperature overnight, then diluted with H2O and extracted with DCM (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. To a solution of crude material (8 g, 15.89 mmol) in ACN (159 mL) at 0° C. was added TEA (6.64 mL, 47.7 mmol) and MsCl (3.64 g, 31.8 mmol) dropwise. The reaction mixture was stirred at 0° C. for 20 min, then diluted with water and extracted with EtOAc (3×). The combined organic extracts were concentrated in vacuo and the residue was purified by flash column chromatography eluted with 0 to 7% MeOH in DCM to provide (7S,10R)-10-[[(dimethylamino)(oxo)acetyl](ethyl)amino]-2-{([(4-fluorobenzyl)amino]carbonyl}-7-methoxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido [1,2-a]azepin-3-yl methanesulfonate, LC-MS: 582.5 (M+1).

Workup

  1. extractionextracted with DCM (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. stirringThe reaction mixture was stirred at 0° C. for 20 min
  6. extractionextracted with EtOAc (3×)
  7. concentrationThe combined organic extracts were concentrated in vacuo
  8. customthe residue was purified by flash column chromatography
  9. washeluted with 0 to 7% MeOH in DCM
  10. customto provide (7S,10R)-10-[[(dimethylamino)(oxo)acetyl](ethyl)amino]-2-{([(4-fluorobenzyl)amino]carbonyl}-7-methoxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido [1,2-a]azepin-3-yl methanesulfonate, LC-MS

Sources & evidence

ORD record
ord-1ee1c55bcd5c4d73808ffa2e2fe47f26
Source dataset
uspto-grants-2013_08
Patent number
US08513234B2

Reaction notes

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