Methanol → HCID 89717657, compound

HRID 1480754Notes

Reaction equation

HRID 1480754 reaction equation
[CH2:1]([C:8]1[N:9]=[C:10](Cl)[C:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([O:22][CH3:23])=[O:21])=[CH:17][CH:18]=3)[NH:13][C:12]=2[N:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:26][CH2:27][CH2:28][CH2:29][N:30]([CH3:35])[CH2:31][CH2:32][CH2:33][NH2:34].CO>>[NH2:26][CH2:27][CH2:28][CH2:29][N:30]([CH3:35])[CH2:31][CH2:32][CH2:33][NH:34][C:10]1[C:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([O:22][CH3:23])=[O:21])=[CH:17][CH:18]=3)[NH:13][C:12]=2[N:24]=[C:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:9]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 7777N,N-bis(3-aminopropyl)methylamineHCID 89717993HCID 89717993, compound

Product 1

HCID 89717657HCID 89717657, compoundYield 67.3%

Conditions

Temperature
140 °C

Procedure

In a 2-5 mL microwave vial was added methyl 2-benzyl-4-chloro-9H-pyrimido[4,5-b]indole-7-carboxylate (0.050 g, 0.142 mmol) and N1-(3-aminopropyl)-N1-methylpropane-1,3-diamine (0.115 mL, 0.711 mmol) in MeOH (2.000 mL, 49.4 mmol) to give a tan suspension. The vial was placed in the microwave and heated to 140° C. for 30 min. After 30 minutes, the mixture was concentrated to dryness on a rotavap. and the residue was purified by flash chromatography and lyophilized from CH3CN to afford two distinct products: Example 45 as the mono-N-alkylated product: methyl 4-((3-((3-aminopropyl)(methyl)amino)propyl)amino)-2-benzyl-9H-pyrimido[4,5-b]indole-7-carboxylate (44 mg, 67.2% yield) as a white solid; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (dt, J=13.8, 6.6 Hz, 2H) 1.72 (dt, J=13.7, 6.8 Hz, 2H) 2.11 (s, 3H) 2.24-2.30 (m, 2H) 2.33 (t, J=6.7 Hz, 2H) 2.47 (br. s., 2H) 3.51-3.61 (m, 2H) 3.76-3.85 (m, 3H) 3.97 (s, 2H) 7.08-7.15 (m, 1H) 7.17-7.24 (m, 2H) 7.27-7.34 (m, 2H) 7.50 (t, J=5.3 Hz, 1H) 7.76 (dd, J=8.2, 1.6 Hz, 1H) 7.92 (d, J=1.6 Hz, 1H) 8.20 (d, J=8.2 Hz, 1H); MS m/z 461.2 (M+H)+; HPLC >99%, RT=1.63 minutes.

Workup

  1. customto give a tan suspension
  2. concentrationthe mixture was concentrated to dryness on a rotavap
  3. customand the residue was purified by flash chromatography
  4. customto afford two distinct products

Sources & evidence

ORD record
ord-066394f6217144b4ae8a74d57ac4c1ab
Source dataset
uspto-grants-2016_08
Patent number
US09409906B2

Reaction notes

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