Methanol → 2-Amino-1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methylpropan-1-one

HRID 2199901Notes

Reaction equation

HRID 2199901 reaction equation
C(Cl)(=O)C.CO.[NH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[N:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[N:23]=[CH:22][C:21]([N:27]3[CH2:32][CH2:31][N:30]([C:33](=[O:45])[C:34]([NH:37]C(=O)OC(C)(C)C)([CH3:36])[CH3:35])[CH2:29][CH2:28]3)=[CH:20]4)=[CH:13][C:11]=2[N:12]=1.C([O-])([O-])=O.[Na+].[Na+]>O>[NH2:37][C:34]([CH3:36])([CH3:35])[C:33]([N:30]1[CH2:31][CH2:32][N:27]([C:21]2[CH:22]=[N:23][C:24]3[C:19]([CH:20]=2)=[N:18][C:17]([C:14]2[CH:15]=[CH:16][C:10]4[O:9][C:8]([NH2:7])=[N:12][C:11]=4[CH:13]=2)=[CH:26][CH:25]=3)[CH2:28][CH2:29]1)=[O:45]

Participants

6

Reactant 4

HCID 887MethanolHCID 6367Acetyl chlorideHCID 10340Sodium CarbonateHCID 70648853Tert-butyl(1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate

Product 1

HCID 546753802-Amino-1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methylpropan-1-oneYield 62.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Acetyl chloride (4.3 mL, 60.5 mmol) was added to MeOH (11 mL) at 0° C., the resulting solution was stirred at 0° C. for 30 min. To this solution, tert-butyl (1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate (D-21) (85 mg, 0.16 mmol, 1.0 eq) was added, and the mixture was stirred at RT for 2 h. The reaction was complete based on TLC analysis. The mixture was diluted with water (20 mL), neutralized with solid Na2CO3 (about 3.5 g) to adjust pH value to 8-9, and extracted with CH2Cl2 (6×30 mL). The combined organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and purified by silica gel column chromatography (11% MeOH/CH2Cl2) to afford the desired product, 2-amino-1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methylpropan-1-one (43) (43 mg, 62.3%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.96 (s, 1H), 8.28 (d, J=8.8 Hz, 1H), 8.12-8.09 (m, 2H), 7.92 (d, J=7.6 Hz, 1H), 7.59 (s, 1H), 7.60-7.47 (m, 3H), 4.01 (m, 4H), 3.42 (m, 4H), 1.347 (s, 6H); ESI-MS m/z: 432.21[M+H]+.

Workup

  1. stirringthe mixture was stirred at RT for 2 h
  2. extractionextracted with CH2Cl2 (6×30 mL)
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompurified by silica gel column chromatography (11% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-c16b56b24b914e269b54725b002e171d
Source dataset
uspto-grants-2016_06
Patent number
US09359352B2

Reaction notes

Loading…