Hydrochloric Acid → HCID 9823143, compound

HRID 1976127Notes

Reaction equation

HRID 1976127 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5](=[O:30])[NH:6][CH2:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[S:16][C:17]3[CH2:24][CH2:23][CH2:22][C:21]4[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:20]=4[C:18]=3[N:19]=2)[CH2:10][CH2:9]1.[H-].[Na+].CCOC(C)=O.Cl>CN(C=O)C.C(Cl)(Cl)Cl.CCOCC.O>[F:29][C:27]1[CH:26]=[CH:25][C:21]2[CH2:22][CH2:23][CH2:24][C:17]3[S:16][C:15]([NH:14][CH:11]4[CH2:12][CH2:13][CH:8]([CH2:7][N:6]5[CH2:2][CH2:3][O:4][C:5]5=[O:30])[CH2:9][CH2:10]4)=[N:19][C:18]=3[C:20]=2[CH:28]=1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8857Ethyl AcetateHCID 24758Sodium hydride2×HCID 22000386HCID 22000386, compound

Product 1

HCID 9823143HCID 9823143, compoundYield 57%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-chloroethyl-N-({4-[(9-fluoro-5,6-dihydro-4H-benzo[6,7]-cyclohepta[d][1,3]thiazol-2-yl)amino]cyclohexyl}methyl)carbamate (5.4 g, 11.95 mmol) in 100 ml anhydrous DMF was added NaH (60% in mineral oil) (0.6 g, 15.0 mmol). TLC (EtOAc) indicated that the reaction had proceeded to approximately 40% completion after 15 minutes. An additional 0.58 g (14.5 mmol) NaH (60% in mineral oil) was added and the solution was stirred at room temperature for another 15 minutes. TLC indicated the reaction was complete. The solution was poured into water (500 ml) and was extracted with EtOAc. The extract was separated and evaporated to yield a dark viscous oil. The oil was chromatographed on silica-gel eluting with 2:1 EtOAc/hexane to yield a white solid. The solid was dissolved in 40 ml CHCl3 and 10 ml 1N HCl in Et2O was added to the solution. The volatiles were removed and the resulting solid was triturated with Et2O. The solution was filtered and the slightly tan solid washed with ether and dried to yield 52% (2.83 g) of the desired product as the HCl salt: 1H-NMR (Free-base) (CDCl3) δ 1.16 (4H, m), 1.60 (1H, m), 1.80 (2H, m), 2.05 (2H, m), 2.22 (2H, m), 2.81 (4H, m), 3.12 (2H, d, J=7.3 Hz), 3.27 (1H, m), 3.57 (2H, t, J=8.2 Hz), 4.33 (2H, t, J=8.0 Hz), 5.05 (1H, d, J=7.7 Hz), 6.83 (1H, dt, J=2.7, 8.2 Hz), 7.05 (1H, m), 7.68 (1H, dd, J=2.7, 10.8 Hz). m.p. (HCl salt) 223-225° C. Anal. Calcd. For C22H27N3ClFO2S: C, 58.5; H, 6.0; N, 9.3. Found: C, 58.43; H, 6.06; N, 9.38; 416 (ESMS, MH+).

Workup

  1. extractionwas extracted with EtOAc
  2. customThe extract was separated
  3. customevaporated
  4. customto yield a dark viscous oil
  5. customThe oil was chromatographed on silica-gel
  6. washeluting with 2:1 EtOAc/hexane
  7. customto yield a white solid
  8. customThe volatiles were removed
  9. customthe resulting solid was triturated with Et2O
  10. filtrationThe solution was filtered
  11. washthe slightly tan solid washed with ether
  12. customdried

Sources & evidence

ORD record
ord-2a42c8deacf040749c1a526e9ef3764a
Source dataset
uspto-grants-2001_05
Patent number
US06225330B1

Reaction notes

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