Methanol → HCID 89719424, compound

HRID 930205Notes

Reaction equation

HRID 930205 reaction equation
[CH2:1]([O:8][CH:9]([C:14]1[CH:15]=[C:16]([CH:36]=[CH:37][CH:38]=1)[CH2:17][C:18]1[N:19]=[C:20](Cl)[C:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:28]=3)[NH:23][C:22]=2[N:34]=1)[C:10]([F:13])([F:12])[F:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:39][CH2:40][CH2:41][CH2:42][N:43]([CH3:48])[CH2:44][CH2:45][CH2:46][NH2:47].CO>>[NH2:39][CH2:40][CH2:41][CH2:42][N:43]([CH3:48])[CH2:44][CH2:45][CH2:46][NH:47][C:20]1[C:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:28]=3)[NH:23][C:22]=2[N:34]=[C:18]([CH2:17][C:16]2[CH:36]=[CH:37][CH:38]=[C:14]([CH:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:10]([F:13])([F:12])[F:11])[CH:15]=2)[N:19]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 7777N,N-bis(3-aminopropyl)methylamineHCID 89719227HCID 89719227, compound

Product 1

HCID 89719424HCID 89719424, compoundYield 63.9%

Conditions

Temperature
140 °C

Procedure

A mixture of methyl 2-(3-(1-(benzyloxy)-2,2,2-trifluoroethyl)benzyl)-4-chloro-9H-pyrimido[4,5-b]indole-7-carboxylate (0.375 g, 0.695 mmol) and N1-(3-aminopropyl)-N1-methylpropane-1,3-diamine (0.784 mL, 4.86 mmol) in MeOH (9.83 mL, 243 mmol) was heated in a microwave oven to 140° C. for 30 minutes. Then, after concentration to dryness under reduced pressure the resulting brown oil was purified by flash chromatography to afford methyl 4-((3-((3-aminopropyl)(methyl)amino)propyl)amino)-2-(3-(1-(benzyloxy)-2,2,2-trifluoroethyl)benzyl)-9H-pyrimido[4,5-b]indole-7-carboxylate (288 mg, 63.9% yield) as a yellow foam: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48 (dt, J=14.0, 6.9 Hz, 2H) 1.75 (quin, J=6.7 Hz, 2H) 2.14 (s, 3H) 2.24-2.42 (m, 4H) 2.52-2.60 (m, 2H) 3.61 (q, J=6.3 Hz, 2H) 3.88 (s, 3H) 4.10 (s, 2H) 4.49 (s, 2H) 5.17 (q, J=7.0 Hz, 1H) 7.18-7.30 (m, 5H) 7.31-7.36 (m, 1H) 7.39 (t, J=7.6 Hz, 1H) 7.44-7.53 (m, 2H) 7.58 (t, J=5.3 Hz, 1H) 7.84 (dd, J=8.2, 1.4 Hz, 1H) 8.00 (d, J=1.4 Hz, 1H) 8.28 (d, J=8.2 Hz, 1H); MS m/z 649.3 (M+H)+; HPLC 97.6% @ 220 nm and 95.5% @ 254 nm, RT=1.96 minutes.

Workup

  1. concentrationThen, after concentration to dryness under reduced pressure the resulting brown oil
  2. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-39d2312151eb42daa3db457c191d4a69
Source dataset
uspto-grants-2016_03
Patent number
US09296744B2

Reaction notes

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