4-Pyridinecarboxaldehyde → (S)-(3-fluoro-5-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 507177Notes

Reaction equation

HRID 507177 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=O)=[CH:3][CH:2]=1.[F:9][C:10]1[CH:11]=[C:12]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:13][N:14]([C:31]1[N:32]=[N:33][N:34]([CH3:36])[N:35]=1)[C@H:15]1[CH2:21][CH2:20][CH2:19][NH:18][C:17]2[CH:22]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:24]([CH3:26])=[CH:25][C:16]1=2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(O)(=O)C.C(Cl)Cl>[F:9][C:10]1[CH:11]=[C:12]([CH:37]=[C:38]([C:40]([F:43])([F:41])[F:42])[CH:39]=1)[CH2:13][N:14]([C@H:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[C:17]2[CH:22]=[C:23]([C:27]([F:28])([F:29])[F:30])[C:24]([CH3:26])=[CH:25][C:16]1=2)[C:31]1[N:32]=[N:33][N:34]([CH3:36])[N:35]=1

Participants

7

Reactant 3

HCID 133894-PyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59432315(S)-(3-fluoro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine-5-yl)-amine

Product 1

HCID 59432360(S)-(3-fluoro-5-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amineYield 87.9%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

Add pyridine-4-carboxaldehyde (0.065 mL, 0.69 mmol) to a solution of (S)-(3-fluoro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine-5-yl)-amine (0.12 g, 0.23 mmol) in 1,2-dichloroethane (10 mL) and acetic acid (0.02 mL) at room temperature under nitrogen and stir for 5 min. Add sodium triacetoxy borohydride (0.29 g, 1.38 mmol) and stir for 12 h. Dilute the mixture with methylene chloride (30 mL) and wash with saturated aqueous sodium bicarbonate solution (2×10 mL). Extract the combined aqueous washes with methylene chloride (20 mL) and wash the combined organic extracts with brine (20 mL) and dry over anhydrous sodium sulfate. Remove the solvents under reduced pressure and purify by silica gel column (gradient eluent, 0-5% MeOH in ethyl acetate) to give the title compound (0.12 g, 87%). MS (ES+): 594 (M+H).

Workup

  1. washwash with saturated aqueous sodium bicarbonate solution (2×10 mL)
  2. extractionExtract the combined aqueous washes with methylene chloride (20 mL)
  3. washwash the combined organic extracts with brine (20 mL)
  4. dry with materialdry over anhydrous sodium sulfate
  5. customRemove the solvents under reduced pressure
  6. custompurify by silica gel column (gradient eluent, 0-5% MeOH in ethyl acetate)

Sources & evidence

ORD record
ord-9990357c258b48f8bf6e4941e100ef81
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…