Acetic Acid → HCID 69938746, compound

HRID 1619365Notes

Reaction equation

HRID 1619365 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13](=[O:24])[N:14]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19][C:15]3=[N:16][C:17]=2[CH:18]=1.[F:25][C:26]([F:31])([F:30])[CH2:27][CH:28]=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13](=[O:24])[N:14]3[CH2:23][CH2:22][N:21]([CH2:28][CH2:27][C:26]([F:31])([F:30])[F:25])[CH2:20][CH2:19][C:15]3=[N:16][C:17]=2[CH:18]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 680283,3,3-TrifluoropropanalHCID 5003444Sodium cyanoborohydrideHCID 58574673HCID 58574673, compound

Product 1

HCID 69938746HCID 69938746, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 8-(2-(pyridin-2-yl)ethynyl)-2,3,4,5-tetrahydro-[1,4]diazepino[7,1-b]quinazolin-11(1H)-one (150 mg, 0.48 mmol), 3,3,3-trifluoropropanal (80 mg, 0.72 mmol), and sodium cyanoborohydride (60 mg, 0.96 mmol) in MeOH (10 mL) was added acetic acid (29 mg, 0.48 mmol). The mixture was stirred for 1 h at room temperature. The reaction mixture was quenched with saturated sodium carbonate solution (30 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4. After filtration and concentration, the crude product was purified by column chromatography to give the desired product. The product was then converted to the corresponding 2HCl salt. MS (ESI): 413 (MH+); 1H NMR (300 MHz, CD3OD) δ 8.94-8.92 (d, J=5.82 Hz, 1H), 8.72-8.66 (t, J=7.98 Hz, 1H), 8.39-8.34 (t, J=9.00 Hz, 2H), 8.15-8.10 (t, J=7.83 Hz, 1H), 8.07 (s, 1H), 7.91-7.88 (d, J=8.22 Hz, 1H), 4.84-4.80 (m, 3H), 3.81-3.71 (m, 5H), 3.66-3.54 (m, 2H), 3.03-2.94 (m, 2H). mGluR5 PAM EC50: ++. Fold shift at 10 μM: +++.

Workup

  1. customThe reaction mixture was quenched with saturated sodium carbonate solution (30 mL)
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-4ee00f0c8829418785515a24c543dce8
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

Loading…