Isocyanate → 1-(3-Methyl-isoquinolin-5-yl)-3-[1-(2-trifluoromethyl-benzyl)pyrrolidin-3-yl]urea

HRID 490291Notes

Reaction equation

HRID 490291 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([NH:12][C:13]([NH:15][CH:16]1[CH2:20][CH2:19][NH:18][CH2:17]1)=[O:14])[CH:8]=[CH:7][CH:6]=2.[F:21][C:22]([F:32])([F:31])[C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH:25]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].[N-]=C=O>ClCCl>[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([NH:12][C:13]([NH:15][CH:16]1[CH2:20][CH2:19][N:18]([CH2:25][C:24]3[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=3[C:22]([F:21])([F:31])[F:32])[CH2:17]1)=[O:14])[CH:8]=[CH:7][CH:6]=2

Participants

7

Reactant 5

HCID 105034IsocyanateHCID 123067o-(Trifluoromethyl)benzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 688557451-(3-Methyl-isoquinolin-5-yl)-3-pyrrolidin-3-yl urea

Product 1

HCID 99323271-(3-Methyl-isoquinolin-5-yl)-3-[1-(2-trifluoromethyl-benzyl)pyrrolidin-3-yl]ureaYield 57.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (D4) (40 mg, 0.15 mmol) and 2-trifluoromethyl benzaldehyde (23 mg, 0.13 mmol) in dichloromethane (5 ml) was stirred at 25° C. for 1 h. Sodium triacetoxyborohydride (32 mg, 0.15 mmol) was added and the reaction stirred for 48 h. A saturated solution of sodium hydrogen carbonate (5 mL) was added and the mixture stirred for 15min. The organic layer was removed, stirred with polymer supported isocyanate resin (2.1 eq.) for 3 h and then filtered. The filtrate was applied to an SCX column and eluted with methanol followed by 2% ammonia in methanol. Evaporation of the solvent in vacuo gave the title compound as a pale yellow solid (32 mg, 56%). 1H NMR (CDCl3) δ: 2.25-2.35 (2H, m), 2.50-2.70 (3H, m), 2.62 (3H, s), 2.80-2.90 (1H, m), 3.67-3.75 (2H, m), 4.30-4.40 (1H, m), 5.35 (1H, d, J=8.1 Hz), 7.25-7.40 (3H, m), 7.45-7.55 (4H, m), 7.70-7.80 (2H, m), 9.16 (1H, s); MS: C23H23N4OF3 requires 428, found 429 (MH+).

Workup

  1. stirringthe reaction stirred for 48 h
  2. stirringthe mixture stirred for 15min
  3. customThe organic layer was removed
  4. stirringstirred with polymer
  5. customfor 3 h
  6. filtrationfiltered
  7. washeluted with methanol
  8. customEvaporation of the solvent in vacuo

Sources & evidence

ORD record
ord-20b30e6c8a64434f98a5ac95dff0f353
Source dataset
uspto-grants-2009_05
Patent number
US07528150B2

Reaction notes

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