1,1'-Carbonyldiimidazole → N-((1H-indol-2-yl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

HRID 2279580Notes

Reaction equation

HRID 2279580 reaction equation
Cl.[NH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][NH2:12].C1N=CN([C:18](N2C=NC=C2)=[O:19])C=1.[O:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:32]2[N:33]=[CH:34][C:35]3[CH2:41][CH2:40][NH:39][CH2:38][C:36]=3[N:37]=2)[CH2:27][CH2:26]1>C(Cl)Cl>[NH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][NH:12][C:18]([N:39]1[CH2:40][CH2:41][C:35]2[CH:34]=[N:33][C:32]([NH:31][CH:28]3[CH2:27][CH2:26][O:25][CH2:30][CH2:29]3)=[N:37][C:36]=2[CH2:38]1)=[O:19]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 45156279(1H-indol-2-yl)methanamine hydrochlorideHCID 71743546N-(tetrahydro-2H-pyran-4-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-amine

Product 1

HCID 60198786N-((1H-indol-2-yl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (1H-indol-2-yl)methanamine hydrochloride (50 mg, 0.27 mmol, CASRN 21109-25-1) and DCM (2.5 mL) at RT were added sequentially TEA (50 μL, 0.36 mmol) and CDI (44 mg, 0.27 mmol) and the reaction was stirred at RT for 30 min. This solution was added to a solution of 28 (55 mg, 0.229 mmol) and TEA (95.7 μL, 0.687 mmol) in DCM (5 mL) and the combined solution was stirred overnight. This solution was loaded directly a SiO2 chromatography column and eluted with a gradient hexane/EtOAc (0 to 10% EtOAc) to afford 57 mg (61.1%) of I-114: 1H NMR (400 MHz, CDCl3) δ 9.28 (s, 1H), 8.07 (s, 1H), 7.54 (d, 1H, J=7.8 Hz), 7.34 (d, 1H, J=7.1 Hz), 7.12-7.17 (m, 1H), 7.04-7.08 (m, 1H), 6.31-6.32 (m, 1H), 4.99-5.03 (m, 1H), 4.87 (d, 1H, J=7.7 Hz), 4.50 (d, 2H, J=5.9 Hz), 4.34 (s, 2H), 3.94-4.04 (m, 3H), 3.65-3.69 (m, 2H), 3.49-3.56 (m, 2H), 2.66-2.71 (m, 2H), 1.98-2.04 (m, 2H), 1.46-1.57 (m, 2H); MS (APCI-pos) M+1=407.4.

Workup

  1. stirringthe combined solution was stirred overnight
  2. washeluted with a gradient hexane/EtOAc (0 to 10% EtOAc)
  3. customto afford 57 mg (61.1%) of I-114

Sources & evidence

ORD record
ord-161b452b731a485cb0d07d9c29aa2d6d
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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