Benzilic acid → HCID 10324628, compound

HRID 1269324Notes

Reaction equation

HRID 1269324 reaction equation
[OH:1][C:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:30][CH2:31][CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][CH:37]([C:40]2[CH:41]=[C:42]([NH:47][C:48](=[O:52])[CH:49]([CH3:51])[CH3:50])[CH:43]=[CH:44][C:45]=2[CH3:46])[CH2:36][CH2:35]1>C(Cl)Cl>[OH:1][C:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([NH:30][CH2:31][CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][CH:37]([C:40]2[CH:41]=[C:42]([NH:47][C:48](=[O:52])[CH:49]([CH3:50])[CH3:51])[CH:43]=[CH:44][C:45]=2[CH3:46])[CH2:36][CH2:35]1)=[O:5]

Participants

5

Reactant 3

HCID 6463Benzilic acidHCID 682631,1'-CarbonyldiimidazoleHCID 16757468N-{3-[1-(aminopropyl)-4-piperidinyl]-4-methylphenyl}-2-methylpropanamide

Product 1

HCID 10324628HCID 10324628, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of hydroxy(diphenyl)acetic acid (100 mg, 0.44 mmol) and 1,1′-carbonyldiimidazole (78 mg, 0.48 mmol) in CH2Cl2 (5 mL) was stirred at room temperature for 3 h, then a solution of N-{3-[1-(3-aminopropyl)-4-piperidinyl]-4-methylphenyl}-2-methyl propanamide (140 mg, 0.44 mmol) in CH2Cl2 (5 mL) was added. The resulting mixture was stirred at room temperature for overnight, evaporated in vacuo, and dissolved in a mixture of EtOAc and 1N NaOH. The organic layer was separated, washed twice with water, dried over MgSO4 and concentrated. The residue was purified over preparative TLC (10% 2M NH3/MeOH in 50% EtOAc/hexane) to give 111 mg (0.21 mmol, 48%) of (N-{3-[1-(3-{[hydroxy(diphenyl)acetyl]amino}propyl)-4-piperidinyl]-4-methylphenyl}-2-methylpropanamide: 1H NMR (400 MHz, CDCl3) δ 9.22 (s, 1 H), 8.14 (s, 1 H), 7.80 (s, 1 H), 7.64–7.48 (m, 4 H), 7.32–7.16 (m, 6 H), 6.95 (d, 1 H, J=8.0 Hz), 6.64 (d, 1 H, J=8.0 Hz), 5.83–5.62 (br, 1 H), 3.54–3.38 (m, 2 H), 3.11–2.94 (m, 2 H), 2.79–2.59 (m, 1 H), 2.57–2.41 (m, 2 H), 2.26 (s, 3 H), 2.29–2.16 (m, 1 H), 2.16–1.91 (m, 4 H), 1.74–1.53 (m, 4 H), 0.86 (d, 6 H, J=6.8 Hz); ESMS m/e: 528.4 (M+H)+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for overnight
  2. customevaporated in vacuo
  3. dissolutiondissolved in a mixture of EtOAc and 1N NaOH
  4. customThe organic layer was separated
  5. washwashed twice with water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified over preparative TLC (10% 2M NH3/MeOH in 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-a76651705f424ec1902c08f3f441df7d
Source dataset
uspto-grants-2007_04
Patent number
US07199135B2

Reaction notes

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