Dimethylformamide → HCID 67376243, compound

HRID 1667196Notes

Reaction equation

HRID 1667196 reaction equation
[OH:1][NH:2]/[C:3](/[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[CH:9]2)=[N:4]\[H].Cl.C(N=C=NCCCN(C)C)C.[O:27]=[C:28]1[C:33]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:32][CH2:31][CH2:30][N:29]1[CH2:46][C:47](O)=O.CN(C)C=O>ClC(Cl)C>[NH:11]1[C:12]2[C:8](=[CH:7][C:6]([C:3]3[N:4]=[C:47]([CH2:46][N:29]4[CH2:30][CH2:31][CH2:32][C:33]([C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[C:28]4=[O:27])[O:1][N:2]=3)=[CH:14][CH:13]=2)[CH:9]=[N:10]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acidHCID 178506489HCID 178506489, compound

Product 1

HCID 67376243HCID 67376243, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

(Z)—N-hydroxy-1H-indazole-5-carboximidamide (0.055 g, 0.312 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.120 g, 0.624 mmol) and 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid (0.097 g, 0.312 mmol; Example 68E) were stirred together in dichloroethane (1 mL) at room temperature for 20 minutes. N,N-Dimethylformamide (0.2 mL) was added and stirring was continued for 2 hours and a dark solution resulted. The reaction was heated to 85° C. and stirred overnight. The reaction was cooled, concentrated, loaded onto a GraceResolv™ 4 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes (Flow=18 mL/minute) over 30 minutes. The material obtained was subjected to a second chromatography on a GraceResolv™ 4 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 0.5% methanol/dichloromethane to 7.5% methanol/dichloromethane (Flow=18 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (s, 1H), 8.30 (s, 1H), 8.01 (dd, J=1.2, 8.8, 1H), 7.75 (d, J=8.7, 1H), 7.45-7.07 (m, 10H), 4.92 (s, 2H), 3.66 (t, J=6.3, 2H), 2.76-2.57 (m, 2H), 1.78 (s, 2H).

Workup

  1. customa dark solution resulted
  2. stirringstirred overnight
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated
  5. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes (Flow=18 mL/minute) over 30 minutes
  6. customThe material obtained
  7. washthe product eluted with a gradient of 0.5% methanol/dichloromethane to 7.5% methanol/dichloromethane (Flow=18 mL/minute) over 30 minutes

Sources & evidence

ORD record
ord-1a37be4bb64840479ffe0a5b0b7238af
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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