Chloroacetyl chloride → HCID 60054738, compound

HRID 489250Notes

Reaction equation

HRID 489250 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@:12]3([C@H:18]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=4)[CH2:17][NH:16][CH2:15]3)[N:11]([CH3:27])[C:10]2=[O:28])[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl[CH2:30][C:31](Cl)=[O:32].CCN(C(C)C)C(C)C.[CH2:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1COCC1.CN(C1C=CN=CC=1)C>[CH2:43]([NH:50][CH2:30][C:31]([N:16]1[CH2:17][C@@H:18]([C:19]2[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=2)[C@:12]2([N:11]([CH3:27])[C:10](=[O:28])[N:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:13]2=[O:14])[CH2:15]1)=[O:32])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 119947544-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile

Product 1

HCID 60054738HCID 60054738, compoundYield 16.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Example 15 (41.5 mg, 0.1 mmol) in 1 ml THF, were added TEA (0.0194 ml, 0.14 mmol) and chloroacetyl chloride (0.0095 ml, 0.12 mmol). After 15 min. at RT, the reaction mixture was evaporated to dryness to yield 47.8 mg of crude intermediate. To this intermediate (37.7 mg, 0.077 mmol) in 1 ml THF, were added PS-DIEA (Argonaut, 21 mg, 0.06 mmol), benzylamine (4.9 μl, 0.045 mmol) and PS-DMAP (Argonaut, 20 mg, 0.06 mmol). The reaction mixture was stirred for 24 h at RT before evaporation to dryness. The residue was purified by reverse phase HPLC (gradient from CH3CN/H2O/TFA: 5/95/0.05 to CH3CN/H2O/TFA: 80/20/0.05) to yield the titled compound (4.2 mg). Retention time: 10.65 min., 563 (M+1); (LCMS conditions: HP 1100 MSD platform (APCI−, DAD (210-400 nm)), Column: TSK gel Super ODS 4.6 mm ID×10 cm, Flow rate: 1 mL/min, Gradient: from 5% to 95% eluent B in 15 min., with a plateau with 95% eluent B during 5 min. Eluent A: H2O (0.1% ammonium formate), Eluent B: CH3CN). 1H NMR (CDCl3): 7.75-7.6 (2H, d), 7.6-7.15 (8H, m), 7.75 (2H, d), 4.25 (2H, s), 4.2-3.6 (7H,m), 3.3-3.05 (3H, m).

Workup

  1. customthe reaction mixture was evaporated to dryness
  2. customto yield 47.8 mg of crude intermediate
  3. customThe residue was purified by reverse phase HPLC (gradient from CH3CN/H2O/TFA: 5/95/0.05 to CH3CN/H2O/TFA: 80/20/0.05)

Sources & evidence

ORD record
ord-efa4f451874d4e5195d57536ce5e83f8
Source dataset
uspto-grants-2005_12
Patent number
US06977267B2

Reaction notes

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