1,1'-Carbonyldiimidazole → (R)-N-(1-(3,4-dichlorophenyl)ethyl)-2-(2-ethoxypyridin-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

HRID 2279497Notes

Reaction equation

HRID 2279497 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([NH2:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].C1N=CN([C:17](N2C=NC=C2)=[O:18])C=1.[CH2:24]([O:26][C:27]1[CH:32]=[C:31]([NH:33][C:34]2[N:35]=[CH:36][C:37]3[CH2:43][CH2:42][NH:41][CH2:40][C:38]=3[N:39]=2)[CH:30]=[CH:29][N:28]=1)[CH3:25].CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([NH:11][C:17]([N:41]2[CH2:42][CH2:43][C:37]3[CH:36]=[N:35][C:34]([NH:33][C:31]4[CH:30]=[CH:29][N:28]=[C:27]([O:26][CH2:24][CH3:25])[CH:32]=4)=[N:39][C:38]=3[CH2:40]2)=[O:18])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 793515(R)-1-(3,4-dichlorophenyl)ethanamineHCID 68294219N-(2-ethoxypyridin-4-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-amine

Product 1

HCID 60198529(R)-N-(1-(3,4-dichlorophenyl)ethyl)-2-(2-ethoxypyridin-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A vial was charged with 185 (0.105 g, 0.553 mmol), CDI (0.0896 g, 0.553 mmol) and DCM (2 mL) and stirred for 30 min. To the solution was added 186 (0.150 g, 0.553 mmol) and DIPEA (0.193 ml, 1.11 mmol) and the resulting reaction stirred for 3 d. The reaction was washed with brine (4 mL), and the organic phase concentrated and loaded on to a preparative SiO2 plate (1.0 mm thickness) which was developed with EtOAc/MeOH (95:5) and eluted to afford 0.038 g (13%) of I-35: 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 7.96 (d, 1H), 7.73 (s, 1H), 7.44 (m, 1H), 7.35 (d, 1H), 7.29 (m, 1H), 7.20 (m, 1H), 6.95 (m, 1H), 5.40 (d, 1H), 5.00 (m, 1H), 4.49 (s, 1H), 4.36 (q, 2H), 3.68 (m, 2H), 2.72 (d, 2h), 1.49 (d, 3H), 1.39 (t, 3H); m/z (APCI-pos) M+1=487.2.

Workup

  1. customthe resulting reaction
  2. stirringstirred for 3 d
  3. washThe reaction was washed with brine (4 mL)
  4. concentrationthe organic phase concentrated
  5. washeluted
  6. customto afford 0.038 g (13%) of I-35: 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 7.96 (d, 1H), 7.73 (s, 1H), 7.44 (m, 1H), 7.35 (d, 1H), 7.29 (m, 1H), 7.20 (m, 1H), 6.95 (m, 1H), 5.40 (d, 1H), 5.00 (m, 1H), 4.49 (s, 1H), 4.36 (q, 2H), 3.68 (m, 2H), 2.72 (d, 2h), 1.49 (d, 3H), 1.39 (t, 3H)

Sources & evidence

ORD record
ord-02e1721bff334693b486ee6ffa3edb30
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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