Triethylamine → 7-(4-(biphenyl-4-ylmethyl)piperazin-1-yl)-3,4-dihydroquinazolin-2(1H)-one

HRID 1520119Notes

Reaction equation

HRID 1520119 reaction equation
[N:1]1([C:7]2[CH:16]=[C:15]3[C:10]([CH2:11][NH:12][C:13](=[O:17])[NH:14]3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:18]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:23]=[CH:22][C:21]([CH:24]=O)=[CH:20][CH:19]=1.CCN(CC)CC.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>CS(C)=O.C(OCC)(=O)C>[C:18]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:19]=[CH:20][C:21]([CH2:24][N:4]2[CH2:5][CH2:6][N:1]([C:7]3[CH:16]=[C:15]4[C:10]([CH2:11][NH:12][C:13](=[O:17])[NH:14]4)=[CH:9][CH:8]=3)[CH2:2][CH2:3]2)=[CH:22][CH:23]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 76689(1,1'-Biphenyl)-4-carboxaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 1177594787-(piperazin-1-yl)-3,4-dihydroquinazolin-2(1H)-one

Product 1

HCID 1177594837-(4-(biphenyl-4-ylmethyl)piperazin-1-yl)-3,4-dihydroquinazolin-2(1H)-oneYield 58%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Representative procedure: To a solution of compound 5 (0.15 g, 0.43 mmol) and biphenyl-4-carbaldehyde (a) (0.1 g, 0.55 mmol) in DMSO (2 mL) at 0° C. was added Et3N (0.13 mL, 0.97 mmol). After being stirred for 0.5 h at room temperature, NaBH(OAc)3 (0.11 g, 0.53 mmol) was added, and the mixture was stirred for 6 h. Sat. NaHCO3 solution (5 mL) was added and stirred for 15 min, followed by the addition of ethyl acetate (20 mL). The organic layer was separated and washed with sat. NaHCO3, brine, and dried over Na2SO4 and evaporated. Column chromatography on silica gel, eluting with methanol:dichloromethane (5:95) and then changing to 10:90 afforded 0.099 g (58%) of compound 5a as an off-white solid, m.p. 134-135° C.; IR (KBr) νmax. cm−1: 3431 (NH), 3062 (Ar—H), 2963 (Alph-H), 1703 (C═O), 1620, 1512, 1430 (C═C), 1221 (C—N), 1168 (C—O). 1H NMR (500 MHz, DMSO-d6) δ=2.71 (m, 4H, 2CH2); 3.14 (m, 4H, 2CH2); 3.68 (s, 2H, CH2); 4.47 (s, 2H, CH2); 6.64 (d, 1H, J=2.3 Hz, aromatic H); 6.68 (d, 1H, J=8.3 Hz, aromatic H); 6.78 (dd, 1H, J=2.2, 8.4 Hz, aromatic H); 7.43-7.48 (m, 5H, aromatic H); 7.58-7.61 (m, 4H, aromatic H); 13C NMR (125.7 MHz, DMSO-d6) δ=43.78 (CH2), 50.11 (CH2), 53.02 (CH2), 62.69 (CH2), 98.21 (aromatic-C), 114.64 (aromatic-C), 115.15 (aromatic-C), 117.28 (aromatic-C), 118.25 (aromatic-C), 127.18 (aromatic-C), 127.28 (aromatic-C), 127.53 (aromatic-C), 127.91 (aromatic-C), 128.97 (aromatic-C), 129.21 (aromatic-C), 130.29 (aromatic-C), 130.57 (aromatic-C), 140.92 (aromatic-C), 147.12 (aromatic-C), 156.34 (C═O). Calculated (%) for C25H26N4O (398.21); C: 75.35, H: 6.58, N: 14.06. found (%); C: 75.28, H: 6.64, N: 13.97.

Workup

  1. stirringthe mixture was stirred for 6 h
  2. stirringstirred for 15 min
  3. customThe organic layer was separated
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. washColumn chromatography on silica gel, eluting with methanol:dichloromethane (5:95)

Sources & evidence

ORD record
ord-c7d0170a82694d82bb1dbe25401be58a
Source dataset
uspto-grants-2015_07
Patent number
US09073900B2

Reaction notes

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