Acetic Acid → HCID 59432301, compound

HRID 507167Notes

Reaction equation

HRID 507167 reaction equation
[C:1](O)(=O)C.[F:5][C:6]([F:50])([F:49])[C:7]1[CH:8]=[C:9]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:10][N:11]([C@H:18]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[C:20]2[C:32]([CH3:41])=[C:33]([C:37]([F:40])([F:39])[F:38])[C:34]([CH3:36])=[CH:35][C:19]1=2)[C:12]1[N:13]=[N:14][N:15]([CH3:17])[N:16]=1.C=O.C([BH3-])#N.[Na+]>C(#N)C.ClCCl>[F:48][C:45]([F:46])([F:47])[C:43]1[CH:42]=[C:9]([CH:8]=[C:7]([C:6]([F:5])([F:49])[F:50])[CH:44]=1)[CH2:10][N:11]([C@H:18]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH:26]2[CH2:27][CH2:28][N:29]([CH3:1])[CH2:30][CH2:31]2)[C:20]2[C:32]([CH3:41])=[C:33]([C:37]([F:38])([F:39])[F:40])[C:34]([CH3:36])=[CH:35][C:19]1=2)[C:12]1[N:13]=[N:14][N:15]([CH3:17])[N:16]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59432401HCID 59432401, compound

Product 1

HCID 59432301HCID 59432301, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Add glacial acetic acid (0.25 mL) over 25 minutes to a solution of (S)-(3,5-bistrifluoromethylbenzyl)-(7,9-dimethyl-1-piperidin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine (Example 160) (0.038 g, 0.057 mmol), 37% aqueous formaldehyde (0.014 mL, 0.189 mmol) and sodium cyanoborohydride (0.011 g, 0.172 mmol) in acetonitrile (2.5 mL) at room temperature under an atmosphere of nitrogen and stir for 18 h. Dilute the reaction with dichloromethane (20 mL) and wash with 2 N sodium hydroxide and brine (10 mL each). Dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with dichloromethane/methanol/concentrated ammonium hydroxide (90:10:1), to provide the title compound as a white crushable foam (0.028 g, 72%). 1H NMR (CDCl3, 500 MHz) δ 1.15-1.70 (m, 4H), 1.83-2.06 (m, 7H), 2.33-2.35 (m, 9H), 2.76-3.03 (m, 5H), 3.24 (br s, 1H), 4.13 (m, 3H), 4.80-4.87 (m, 1H), 5.14 (br s, 1H), 5.58 (br s, 1H), 6.58 (m, 1H), 7.77-7.78 (m, 3H); ESI MS m/z 678 [C31H36F9N7+H]+.

Workup

  1. additionDilute
  2. washwash with 2 N sodium hydroxide and brine (10 mL each)
  3. dry with materialDry the organic layer over sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue
  7. washeluting with dichloromethane/methanol/concentrated ammonium hydroxide (90:10:1)

Sources & evidence

ORD record
ord-1444b3e80073401b841655d9409b7254
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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