Sodium triacetoxyborohydride → HCID 59239276, compound

HRID 1698047Notes

Reaction equation

HRID 1698047 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH3:29])[C:16]3[CH2:22][CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].[N:30]1[CH:35]=[CH:34][CH:33]=[C:32]([CH2:36]N2CCC(=O)CC2)[CH:31]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH3:29])[C:16]3[CH2:22][CH2:21][N:20]([CH2:36][C:32]4[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=4)[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 64216241-(pyridin-3-ylmethyl)piperidin-4-oneHCID 46913570Urea, N-ethyl-N'-[4-[5,6,7,8-tetrahydro-4-[(3S)-3-Methyl-4-Morpholinyl]pyrido[3,4-d]pyriMidin-2-yl]phenyl]-

Product 1

HCID 59239276HCID 59239276, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

(S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (0.0995 g, 0.251 mmol) in dry was added 1-(pyridin-3-ylmethyl)piperidin-4-one (0.0486 g, 0.255 mmol). The reaction mixture was then heated at 70° C. for 40 min. The reaction mixture was then cooled at 0° C. and added Sodium triacetoxyborohydride (0.1118 g, 0.5275 mmol). The reaction mixture was allowed to warm slowly to room temperature and stirred for 3 days. The reaction mixture was diluted with water, extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, evaporated, chromatographed through silica gel (12 g, 0-10% MeOH in dichloromethane followed by 6:2:1:1 EtOAc:acetone:water:MeOH), and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.61 (s, 1H), 8.49 (d, J=1.7, 1H), 8.46 (dd, J=4.8, 1.6, 1H), 8.15 (d, J=8.8, 2H), 7.71 (d, J=7.8, 1H), 7.46 (d, J=8.8, 2H), 7.36 (dd, J=7.7, 4.8, 1H), 6.15 (t, J=5.6, 1H), 4.12 (d, J=6.5, 1H), 3.91-3.81 (m, 1H), 3.77-3.53 (m, 6H), 3.50 (s, 2H), 3.45-3.34 (m, 1H), 3.17-3.06 (m, 2H), 2.86 (d, J=11.0, 2H), 2.81-2.71 (m, 1H), 2.70-2.56 (m, 3H), 2.39 (t, J=11.3, 1H), 2.01 (t, J=10.8, 2H), 1.83 (s, 2H), 1.60-1.42 (m, 2H), 1.22 (d, J=6.6, 3H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+571.3 (M+H)+.

Workup

  1. temperatureThe reaction mixture was then cooled at 0° C.
  2. temperatureto warm slowly to room temperature
  3. extractionextracted three times with 10% MeOH in dichloromethane
  4. dry with materialdried over Magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed through silica gel (12 g, 0-10% MeOH in dichloromethane followed by 6:2:1:1 EtOAc:acetone:water:MeOH)
  8. custompurified by HPLC

Sources & evidence

ORD record
ord-ef81c8e276ac417a9c1cb58eb3ec6478
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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