Diisopropylethylamine → Ethyl N-({[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]amino}carbonyl)-beta-alaninate

HRID 1715291Notes

Reaction equation

HRID 1715291 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:8]2[N:9]=[C:10]([CH2:13][C:14]#[N:15])[S:11][CH:12]=2)=[C:5]([CH3:7])[N:6]=1.C(N(CC)C(C)C)(C)C.[N:25]([CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]=[O:27]>C(Cl)Cl>[C:14]([CH2:13][C:10]1[S:11][CH:12]=[C:8]([C:4]2[S:3][C:2]([NH:1][C:26]([NH:25][CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:27])=[N:6][C:5]=2[CH3:7])[N:9]=1)#[N:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2733373Ethyl 3-isocyanatopropanoate2×HCID 59465553(2'-Amino-4'-methyl-4,5'-bi-1,3-thiazol-2-yl)acetonitrile

Product 1

HCID 11990227Ethyl N-({[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]amino}carbonyl)-beta-alaninate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

(2′-Amino-4′-methyl-4,5′-bi-1,3-thiazol-2-yl)acetonitrile, prepared in Step I, described above (236.3 mg; 1 mmol; 1 eq.), is suspended in DCM (5 ml). N,N-Diisopropylethylamine (377 μl; 2.20 mmol; 2.20 eq.) is added, followed by a solution of ethyl 3-isocyanatopropionate (143.1 mg; 1 mmol; 1 eq.) in DCM (3 ml). The reaction mixture is heated at 50° C. overnight. As the reaction is not complete, a second batch of ethyl 3-isocyanatopropionate (Aldrich) (143.1 mg; 1 mmol; 1 eq.) is added. After 36 hours the reaction is complete. The solvents are evaporated. EtOAc is added and the mixture is washed with brine, dried over MgSO4 and evaporated. The resulting crude product is purified by preparative HPLC, affording Compound (50) as white-off solid (76.6 mg; 20%). 1H NMR (DMSO-d6, 300 MHz) δ 1.21 (t, J=7.5 Hz, 3H), 2.44 (s, 3H), 2.58 (m, 2H), 3.39 (q, J=6 Hz, 2H), 4.10 (q, J=7.5 Hz, 2H), 4.62 (s, 2H), 6.72 (t, J=6 Hz, 1H), 7.64 (s, 1H), 10.49 (br s, 1H). M− (ESI): 378.17; M+ (ESI): 380.10. HPLC (method A), Rt: 2.60 min (purity: 100%).

Workup

  1. customThe solvents are evaporated
  2. additionEtOAc is added
  3. washthe mixture is washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe resulting crude product is purified by preparative HPLC

Sources & evidence

ORD record
ord-0c873a0268d44729a59c16480b6f0c1d
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

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