Triethylamine → HCID 178426913, compound

HRID 80703

Reaction equation

HRID 80703 reaction equation
[NH2:1][C:2]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][N:4]1[C:11](=[O:29])[C:12]([OH:28])=[C:13]([C:15]3[NH:16][CH:17]=[C:18]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[N:19]=3)[N:14]=[C:3]21.C(N(CC)CC)C.[CH3:37][C:38]1[O:42][N:41]=[C:40]([C:43](Cl)=[O:44])[CH:39]=1.CNC.CO>C(Cl)Cl.CO>[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:18]2[N:19]=[C:15]([C:13]3[N:14]=[C:3]4[C:2]5([NH:1][C:43]([C:40]6[CH:39]=[C:38]([CH3:37])[O:42][N:41]=6)=[O:44])[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10]5)[CH2:5][N:4]4[C:11](=[O:29])[C:12]=3[OH:28])[NH:16][CH:17]=2)=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27368945-Methylisoxazole-3-carbonyl chlorideHCID 22497844Dimethylamine methanolHCID 178507110HCID 178507110, compound2×

Product 1

HCID 178426913HCID 178426913, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 10-amino-2-(4-(4-fluorobenzyl)-1H-imidazol-2-yl)-3-hydroxy-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one, Example 1 (30 mg, 0.076 mmol) in CH2Cl2 (3 mL) was added triethylamine (0.063 mL, 0.455 mmol) followed by 5-methylisoxazole-3-carbonyl chloride (55.2 mg, 0.379 mmol) and the resulting mixture stirred at room temperature. After 16 h the reaction mixture was concentrated to give the crude product which was treated with 2M dimethylamine/MeOH (0.5 mL) in MeOH (2 mL) at 60° C. for 2 h. The mixture was then cooled and purified by preparative HPLC to afford the title compound (15 mg, 39%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 13.4 (1H, br. s.), 9.0 (1H, s), 7.4 (1H, br. s.), 7.4 (2H, dd, J=8.24, 5.80 Hz), 7.2 (2H, t, J=8.85 Hz), 6.6 (1H, s), 4.1 (2H, d, J=3.36 Hz), 4.1 (2H, s), 2.7-2.8 (2H, m), 2.5 (1H, br. s.), 2.0-2.0 (2H, m), 1.9-1.9 (2H, m), 1.7-1.8 (2H, m). LCMS (M+H)=505.49.

Workup

  1. concentrationAfter 16 h the reaction mixture was concentrated
  2. customto give the crude product which
  3. temperatureThe mixture was then cooled
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-6047d6fde9384728a95dd8b5987bf0a5
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Linked notes

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