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

HRID 1715277Notes

Reaction equation

HRID 1715277 reaction equation
F[C:2](F)(F)[C:3]([O-:5])=[O:4].[CH3:8][C:9]1[N:10]=[C:11]([NH2:27])[S:12][C:13]=1[C:14]1[N:15]=[C:16]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[S:17][CH:18]=1.[CH:28](N(CC)C(C)C)(C)[CH3:29].[N:37]([CH:40](C)C(OCC)=O)=[C:38]=[O:39]>C(Cl)Cl.CCOC(C)=O>[CH3:8][C:9]1[N:10]=[C:11]([NH:27][C:38]([NH:37][CH2:40][CH2:2][C:3]([O:5][CH2:28][CH3:29])=[O:4])=[O:39])[S:12][C:13]=1[C:14]1[N:15]=[C:16]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[S:17][CH:18]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 84468TrifluoroacetateHCID 550681Ethyl 2-isocyanatopropionateHCID 866219884'-Methyl-2-(morpholin-4-ylcarbonyl)-4,5'-bi-1,3-thiazol-2'-amine

Product 1

HCID 11989986Ethyl N-({[4'-methyl-2-(morpholin-4-ylcarbonyl)-4,5-bi-1,3-thiazol-2'-yl]amino}carbonyl)-beta-alaninate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Trifluoroacetate salt of 4′-Methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-amine, prepared as in Step II of Example 36, described above, (150 mg; 0.35 mmol; 1 eq.) is suspended in DCM (5 ml). N,N-Diisopropylethylamine (133 μl; 0.78 mmol; 2.20 eq.) is added. A solution of ethyl 2-isocyanatopropionate (Aldrich)(50.6 mg; 0.35 mmol; 1 eq.) in DCM (3 ml) is added and the resulting mixture is heated at 50° C. overnight. EtOAc is added (10 ml) and the mixture is washed with water. Organic phase is dried over MgSO4 and concentrated. The crude mixture is resubmitted to the same reaction conditions. After one night at 50° C., the conversion is complete and a similar work-up is performed. The crude product is recrystallized in MeOH, affording Compound (37) as white-off powder (92.2 mg; 58%). 1H NMR (DMSO-d6, 300 MHz) δ 1.18 (t, J=6 Hz, 3H), 2.41 (s, 3H), 2.50 (m, 2H), 3.36 (m, 2H), 3.68 (m, 6H), 4.07 (q, J=6 Hz, 2H), 4.33 (m, 2H), 6.70 (br s, 1H), 7.90 (s, 1H), 10.52 (br s, 1H). M− (ESI): 452.14; M+ (ESI): 454.11. HPLC (method A), Rt: 2.89 min (purity: 98.9%).

Workup

  1. washthe mixture is washed with water
  2. dry with materialOrganic phase is dried over MgSO4
  3. concentrationconcentrated
  4. customThe crude mixture is resubmitted to the same reaction conditions
  5. waitAfter one night at 50° C.
  6. customThe crude product is recrystallized in MeOH

Sources & evidence

ORD record
ord-af3419a7c38f446cb2224376d25fca57
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

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