Acetaldehyde → HCID 71657866, compound

HRID 624324Notes

Reaction equation

HRID 624324 reaction equation
[NH2:1][C:2]1[C:29]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[C:32]([C:38](=[O:49])[NH:39][C:40]3([C:43]4[N:48]=[CH:47][CH:46]=[CH:45][N:44]=4)[CH2:42][CH2:41]3)[CH:31]=2)=[CH:28][C:5]2[C:6]([C:16]3[N:17](C(OC(C)(C)C)=O)[CH:18]=[CH:19][N:20]=3)=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1.N[C:51]1C(C2C=CC(OC)=C(C=2)C(NC2(C3N=CC=CN=3)CC2)=O)=CC2C(C3NC=CN=3)=C(C3C=CC(F)=CC=3)OC=2[CH:52]=1.C(=O)C.C([BH3-])#N.[Na+]>CO>[CH2:51]([NH:1][C:2]1[C:29]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[C:32]([CH:31]=2)[C:38]([NH:39][C:40]2([C:43]3[N:44]=[CH:45][CH:46]=[CH:47][N:48]=3)[CH2:42][CH2:41]2)=[O:49])=[CH:28][C:5]2[C:6]([C:16]3[NH:17][CH:18]=[CH:19][N:20]=3)=[C:7]([C:9]3[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=3)[O:8][C:4]=2[CH:3]=1)[CH3:52]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86691634HCID 86691634, compoundHCID 86691635HCID 86691635, compound

Product 1

HCID 71657866HCID 71657866, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

The above obtained mixture of tert-butyl 2-(6-amino-2-(4-fluorophenyl)-5-(4-methoxy-3-((1-(pyrimidin-2-yl)cyclopropyl)carbamoyl)phenyl)benzofuran-3-yl)-1H-imidazole-1-carboxylate and 5-(6-amino-2-(4-fluorophenyl)-3-(1H-imidazol-2-yl)benzofuran-5-yl)-2-methoxy-N-(1-(pyrimidin-2-yl)cyclopropyl)benzamide (170 mg, 0.257 mmol) in MeOH (25 mL) was cooled to 0° C. and then added with acetaldehyde (45.3 mg, 1.029 mmol). The reaction mixture was allowed to warm to rt and stirred for 45 min. The reaction mixture was again cooled to 0° C. and then added with sodium cyanoborohydride (32.3 mg, 0.515 mmol). The reaction mixture was allowed to warm to rt and stirring continued at rt for 2 hr. The reaction mixture was concentrated completely at reduced pressure at 35° C. The residue was diluted with water and 10% NaHCO3 solution, filtered, and the solid obtained dried under suction. The crude product was purified by preparative HPLC to separate the two compounds. 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.32 (br s, 1H) 8.92 (s, 1H) 8.69 (d, J=4.8 Hz, 2H) 7.94-8.03 (m, 2H) 7.86 (d, J=2.51 Hz, 1H) 7.55 (dd, J=8.53, 2.51 Hz, 1H) 7.22-7.33 (m, 5H) 7.21 (s, 1H) 7.13 (s, 1H) 6.91 (s, 1H) 4.58 (t, J=5.65 Hz, 1H) 3.99 (s, 3H) 3.13-3.22 (m, 2H) 1.59-1.66 (m, 2H) 1.38-1.46 (m, 2H) 1.10-1.21 (m, 3H). 19F NMR (376.6 MHz, DMSO-d6) δ ppm: 112.76. LCMS: (ES−) m/z=587.2 (M−H); Column—Acentis Express C8 (50×2.1 mm; 2.7 u); M phase A: 2% MeCN-98% H2O-10 mM NH4COOH; M phase B: 98% MeCN-2% H2O-10 mM NH4COOH

Workup

  1. customThe above obtained
  2. temperatureto warm to rt
  3. temperatureThe reaction mixture was again cooled to 0° C.
  4. temperatureto warm to rt
  5. stirringstirring
  6. waitcontinued at rt for 2 hr
  7. concentrationThe reaction mixture was concentrated completely at reduced pressure at 35° C
  8. additionThe residue was diluted with water and 10% NaHCO3 solution
  9. filtrationfiltered
  10. customthe solid obtained
  11. customdried under suction
  12. customThe crude product was purified by preparative HPLC
  13. customto separate the two compounds

Sources & evidence

ORD record
ord-b0d75335354343a0b4c821b9c10885a6
Source dataset
uspto-grants-2016_04
Patent number
US09303020B2

Reaction notes

Loading…