2-Chloro-N,N-dimethylethylamine → HCID 24758152, compound

HRID 1711320Notes

Reaction equation

HRID 1711320 reaction equation
[C:1]1([C:7]2[CH:12]=[C:11]([C:13]3[NH:17][N:16]=[N:15][N:14]=3)[CH:10]=[CH:9][C:8]=2[NH:18][C:19]([C:21]2[NH:22][C:23]([C:26]#[N:27])=[CH:24][N:25]=2)=[O:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:36][CH2:37][N:38]([CH3:40])[CH3:39].Cl[CH2:42][CH2:43][N:44]([CH3:46])[CH3:45].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:1]1([C:7]2[CH:12]=[C:11]([C:13]3[N:17]([CH2:36][CH2:37][N:38]([CH3:40])[CH3:39])[N:16]=[N:15][N:14]=3)[CH:10]=[CH:9][C:8]=2[NH:18][C:19]([C:21]2[N:22]([CH2:42][CH2:43][N:44]([CH3:46])[CH3:45])[C:23]([C:26]#[N:27])=[CH:24][N:25]=2)=[O:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

8

Reactant 5

HCID 79012-Chloro-N,N-dimethylethylamine2×HCID 11430Potassium Carbonate2×HCID 81531DiisopropylethylamineHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 178510344HCID 178510344, compound

Product 1

HCID 24758152HCID 24758152, compoundYield 21.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-cyano-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(1H-tetrazol-5-yl)-phenyl]-amide (as prepared in Example 57, step (e), 37 mg, 0.10 mmol) in DMF (0.5 mL) was added K2CO3 (42 mg, 0.30 mmol) followed by 2-chloro-ethyl-dimethyl-amine hydrochloride salt (18 mg, 0.12 mmol). The reaction was heated to 70° C. After 3 h, 2-chloro-ethyl-dimethyl-amine (14.6 mg, 0.102 mmol) was again added, followed by K2CO3 (28 mg, 0.20 mmol) and the resulting mixture heated to 100° C. After 1 h, 2-chloro-ethyl-dimethyl-amine (18 mg, 0.12 mmol) and DIEA (35 μL, 0.20) were added and the resulting mixture stirred at 100° C. overnight. The mixture was poured into EtOAc (20 mL) and washed with saturated aqueous NaHCO3 (2×10 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by preparative TLC (15% MeOH—CHCl3) afforded 10.7 mg (21%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 9.85 (s, 1H), 8.44 (d, 1H, J=8.5 Hz), 7.98 (dd, 1H, J=8.5, 2.0 Hz), 7.89 (d, 1H, J=1.9 Hz), 7.66 (s, 1H), 5.84 (m, 1H), 4.67 (t, 2H, J=6.7 Hz), 4.60 (t, 2H, J=5.9 Hz), 2.92 (t, 2H, J=6.7 Hz), 2.68 (t, 2H, J=5.9 Hz), 2.25 (s, 6H), 2.22 (s, 6H), 1.81-1.73 (m, 8H). Mass spectrum (ESI, m/z): Calcd. for C26H34N10O, 503.2, found 503.2.

Workup

  1. temperaturethe resulting mixture heated to 100° C
  2. waitAfter 1 h
  3. washwashed with saturated aqueous NaHCO3 (2×10 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by preparative TLC (15% MeOH—CHCl3)

Sources & evidence

ORD record
ord-ffb339556a46436fa707f25c0518198f
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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