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 930153Notes

Reaction equation

HRID 930153 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-1f32ae2729ce4b39a865a447bf9344d5
Source dataset
uspto-grants-2016_03
Patent number
US09296726B2

Reaction notes

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