Dimethylformamide → HCID 67177913, compound

HRID 1698009Notes

Reaction equation

HRID 1698009 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].CN(C)C=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.Cl.[CH2:44]([NH:46][C:47]([NH:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]2[N:57]=[C:58]([N:66]3[CH2:71][CH2:70][O:69][CH2:68][C@@H:67]3[CH3:72])[C:59]3[CH2:65][NH:64][CH2:63][CH2:62][C:60]=3[N:61]=2)=[CH:52][CH:51]=1)=[O:48])[CH3:45]>>[C:1]([CH2:3][C:4]([N:64]1[CH2:63][CH2:62][C:60]2[N:61]=[C:56]([C:53]3[CH:52]=[CH:51][C:50]([NH:49][C:47]([NH:46][CH2:44][CH3:45])=[O:48])=[CH:55][CH:54]=3)[N:57]=[C:58]([N:66]3[CH2:71][CH2:70][O:69][CH2:68][C@@H:67]3[CH3:72])[C:59]=2[CH2:65]1)=[O:6])#[N:2]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 9740Cyanoacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67276185HCID 67276185, compound

Product 1

HCID 67177913HCID 67177913, compound

Conditions

Temperature
40 °C

Procedure

Cyanoacetic acid (0.0300 g, 0.000353 mol) in dry N,N-Dimethylformamide (1.60 mL, 0.0207 mol) was added 1-Hydroxybenzotriazole (0.0488 g, 0.000361 mol) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.0721 g, 0.000376 mol) then followed by N,N-Diisopropylethylamine (0.161 mL, 0.000924 mol) and then (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)urea hydrochloride (0.1000 g, 0.0002310 mol). The reaction mixture heated at 40° C. and was stirred for 4 days. The reaction mixture was concentrated, chromatographed through silica gel again (12 g, 0-10% MeOH in dichloromethane), and purified by HPLC. 1H NMR (500 MHz, DMSO) δ 8.69 (s, 1H), 8.18 (d, J=8.8, 2H), 7.48 (d, J=8.8, 2H), 6.18 (t, J=5.6, 1H), 4.65 (d, J=15.7, 1H), 4.51-4.38 (m, 1H), 4.26-4.14 (m, 2H), 3.96-3.84 (m, 2H), 3.80-3.56 (m, 5H), 3.44 (dd, J=19.8, 12.6, 2H), 3.15-3.07 (m, 2H), 3.02-2.94 (m, 1H), 2.84 (s, 1H), 1.25 (t, J=5.4, 3H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+464.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customchromatographed through silica gel again (12 g, 0-10% MeOH in dichloromethane)
  3. custompurified by HPLC

Sources & evidence

ORD record
ord-0a67cdfd126d4a2fa209f71383f3cf31
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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