Nitrogen → 1-(4-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-3-hydroxymethyl-benzyl)-3-(1H-imidazol-2-yl)-urea

HRID 251300

Reaction equation

HRID 251300 reaction equation
S(O)(O)(=O)=[O:2].[NH2:6][C:7]1[NH:8][CH:9]=[CH:10][N:11]=1.N#N.CC[N:16]([CH:20](C)C)C(C)C.NC[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:34][N:35]([CH2:46][C:47]2[C:52]([CH3:53])=[CH:51][C:50]([CH3:54])=[CH:49][N:48]=2)[CH:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:39][CH2:38][CH2:37]2)=[C:30]([CH2:32][OH:33])[CH:31]=1>C(Cl)Cl>[CH3:53][C:52]1[C:47]([CH2:46][N:35]([CH2:34][C:29]2[CH:28]=[CH:27][C:26]([CH2:25][NH:16][C:20]([NH:6][C:7]3[NH:8][CH:9]=[CH:10][N:11]=3)=[O:2])=[CH:31][C:30]=2[CH2:32][OH:33])[CH:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:39][CH2:38][CH2:37]2)=[N:48][CH:49]=[C:50]([CH3:54])[CH:51]=1

Participants

6

Reactant 4

HCID 947Nitrogen2×HCID 81531DiisopropylethylamineHCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 67272611(5-Aminoethyl-2-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-phenyl)-methanol

Product 1

HCID 672730331-(4-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-3-hydroxymethyl-benzyl)-3-(1H-imidazol-2-yl)-ureaYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-carbonyldiimidazole (117 mg, 0.72 mmol) dissolved in CH2Cl2 (10 mL) add 2-aminoimidazole sulfate (95 mg, 0.72 mmol). The solution was stirred for 16 hours under a positive pressure of N2. The reaction mixture was concentrated in vacuo and redissolved in DMF (10 mL). Addition of DIPEA (250 ul, 1.44 mmol) and (5-aminoethyl-2-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-phenyl)-methanol (100 mg, 0.24 mmol) was made to the solution. The solution was stirred at 75° C. for 16 hours under a positive pressure of N2. The solution was concentrated in vacuo and redissolved in CH2Cl2 (20 mL). The reaction mixture was quenched with a solution of saturated NaHCO3 (20 mL). Extract with CH2Cl2 (3×25 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a light yellow oil. Purification via column chromatography on silica gel (CH2Cl2:MeOH, 97:3, v/v) afforded the product as a colorless oil (20 mg, 16%). 1H NMR (CDCl3) δ 1.55 (m, 1H), 2.05 (m, 3H), 2.18 (s, 3H), 2.24 (s, 3H), 2.77 (m, 2H), 3.61 (m, 1H), 3.67 (d, 1H, J=11.4 Hz), 3.72 (d, 1H, J=12.7 Hz), 3.83 (m, 1H), 4.11 (m, 2H), 4.35 (m, 3H), 6.59 (s, 2H), 7.23 (m, 5H), 7.66 (s, 1H), 8.16 (s, 1H), 8.31 (m, 1H). ES-MS m/z 526 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in DMF (10 mL)
  3. concentrationThe solution was concentrated in vacuo
  4. dissolutionredissolved in CH2Cl2 (20 mL)
  5. customThe reaction mixture was quenched with a solution of saturated NaHCO3 (20 mL)
  6. extractionExtract with CH2Cl2 (3×25 mL)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford a light yellow oil
  11. customPurification via column chromatography on silica gel (CH2Cl2

Sources & evidence

ORD record
ord-d528c625cccb4dbb894c0167b5f68f30
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Linked notes

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