Water → HCID 9888229, compound

HRID 1976128Notes

Reaction equation

HRID 1976128 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]2[S:11][C:12]3[CH2:19][CH2:18][CH2:17][C:16]4[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:15]=4[C:13]=3[N:14]=2)[CH2:5][CH2:4]1.[CH3:25][O:26][CH2:27][C:28](Cl)=[O:29].O>N1C=CC=CC=1.C(N(C(C)C)CC)(C)C>[F:24][C:22]1[CH:21]=[CH:20][C:16]2[CH2:17][CH2:18][CH2:19][C:12]3[S:11][C:10]([NH:9][CH:6]4[CH2:7][CH2:8][CH:3]([CH2:2][NH:1][C:28](=[O:29])[CH2:27][O:26][CH3:25])[CH2:4][CH2:5]4)=[N:14][C:13]=3[C:15]=2[CH:23]=1

Participants

6

Reactant 3

HCID 962WaterHCID 96623Methoxyacetyl chlorideHCID 178511277HCID 178511277, compound

Product 1

HCID 9888229HCID 9888229, compoundYield 88.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a stirred, septum capped solution of trans-N2-[4-(aminomethyl)cyclohexyl]-9-fluoro-5,6-dihydro-4H-benzo[6,7]cyclohepta[d][1,3]thiazol-2-amine (5.00 g, 11.95 mmol) in anhydrous pyridine (20 ml) and diisopropylethylamine (10 ml) was added methoxyacetyl chloride (1.20 ml, 13.1 mmol) dropwise. The solution was stirred at room temperature for 2 hours and was then poured into 250 ml water and extracted with 250 ml EtOAc. The extract was evaporated to yield a golden viscous oil which was chromatographed on silica-gel eluting with EtOAc to yield 88% (4.40 g) of the desired product as a slightly yellow solid. A small portion of the product was recrystallized from EtOAc (m.p. 95-97° C.). The free-base was dissolved in 60 ml CHCl3 and converted to its HCl salt by adding 14.0 ml 1.0 N HCl in ether followed by evaporation of the solvent. The resulting foam was stirred with ether (75 ml), filtered and washed with ether to yield the HCl salt as a solid: 1H-NMR (Free-base) (CDCl3) δ 1.12 (4H, m), 1.45 (1H, m), 1.81 (2H, m), 2.05 (2H, m), 2.21 (2H, m), 2.80 (4H, m), 3.16 (2H, t, J=6.5 Hz), 3.25 (1H, m), 3.41 (3H, s), 3.89 (2H, s), 5.03 (1H, d, J=8.0 Hz), 6.62 (1H, broad t), 6.81 (1H, dt, J=2.9, 8.3 Hz), 7.03 (1H, m), 7.69 (1H, dd, J=2.8, 10.8 Hz). m.p. 63-65° C. Anal. Calcd. For C22H29N3O2SFCl+0.5CHCl3: C, 52.61; H, 5.79; N, 8.18. Found: C, 52.61; H, 5.92; N, 8.08; 418 (ESMS, MH+).

Workup

  1. extractionextracted with 250 ml EtOAc
  2. customThe extract was evaporated
  3. customto yield a golden viscous oil which
  4. customwas chromatographed on silica-gel
  5. washeluting with EtOAc

Sources & evidence

ORD record
ord-3a1e298a313243fc9d2b538f5e26a3f4
Source dataset
uspto-grants-2001_05
Patent number
US06225330B1

Reaction notes

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