1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-Cyano-1H-pyrrole-2-carboxylic acid [2-cyclohept-1-enyl-4-(1,3-dimethyl-2-oxo-hexahydro-pyrimidin-5-yl)-phenyl]-amide

HRID 2219626Notes

Reaction equation

HRID 2219626 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][N:12]([CH3:14])[C:11](=[O:15])[N:10]([CH3:16])[CH2:9]2)=[CH:4][C:3]=1[C:17]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1.[C:24]([C:26]1[CH:27]=[C:28]([C:31](O)=[O:32])[NH:29][CH:30]=1)#[N:25].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:17]1([C:3]2[CH:4]=[C:5]([CH:8]3[CH2:9][N:10]([CH3:16])[C:11](=[O:15])[N:12]([CH3:14])[CH2:13]3)[CH:6]=[CH:7][C:2]=2[NH:1][C:31]([C:28]2[NH:29][CH:30]=[C:26]([C:24]#[N:25])[CH:27]=2)=[O:32])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 118048114-cyano-1H-pyrrole-2-carboxylic acidHCID 597712785-(4-Amino-3-cyclohept-1-enyl-phenyl)-1,3-dimethyl-tetrahydro-pyrimidin-2-one

Product 1

HCID 247836174-Cyano-1H-pyrrole-2-carboxylic acid [2-cyclohept-1-enyl-4-(1,3-dimethyl-2-oxo-hexahydro-pyrimidin-5-yl)-phenyl]-amideYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(4-amino-3-cyclohept-1-enyl-phenyl)-1,3-dimethyl-tetrahydro-pyrimidin-2-one (as prepared in Example 9, step (a), 21 mg, 0.067 mmol), 4-cyanopyrrolecarboxylic acid (Canadian J. Chem. 59: 2673 (1981)). (24.6 mg, 0.180 mmol), EDCI (19.4 mg, 0.101 mmol), HOBt (9.2 mg, 0.068 mmol), DIEA (35 μL, 0.20 mmol) in DCM (0.5 mL) was stirred at RT overnight. The reaction mixture was concentrated in vacuo and the residue was purified RP-HPLC eluting with 20% to 100% CH3CN in 0.1% TFA/H2O over 20 min on a C18 column to obtain the title compound (4.2 mg, 14%): 1H-NMR (CD3OD; 400 MHz): δ 7.58 (d, 1H, J=1.5 Hz), 7.44 (d, 1H, J=8.2 Hz), 7.15-7.24 (m, 3H), 5.93 (t, 1H, J=6.5 Hz), 3.38-3.61 (m, 5H), 2.96 (m, 6H), 2.48 (m, 2H), 2.28 (m, 2H), 1.82 (m, 2H), 1.45-1.23 (m, 4H); Mass spectrum (ESI, m/z): Calcd. for C25H29N5O2, 432.2 (M+H). found 432.2.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was purified RP-HPLC
  3. washeluting with 20% to 100% CH3CN in 0.1% TFA/H2O over 20 min on a C18 column

Sources & evidence

ORD record
ord-510bfabc43674d4884748e00c445d574
Source dataset
uspto-grants-2008_08
Patent number
US07414050B2

Reaction notes

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