Cyclopentylamine → HCID 58459108, compound

HRID 2036609Notes

Reaction equation

HRID 2036609 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:15]([CH:16]3[CH2:18][CH2:17]3)[C:14]3[C:19]([C:23]([OH:25])=O)=[CH:20][CH:21]=[CH:22][C:13]=3[N:12]=2)[CH3:10])[C:3]=1[C:26]#[N:27].[CH:28]1([NH2:33])[CH2:32][CH2:31][CH2:30][CH2:29]1.C(N(C(C)C)C(C)C)C.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:15]([CH:16]3[CH2:17][CH2:18]3)[C:14]3[C:19]([C:23]([NH:33][CH:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[O:25])=[CH:20][CH:21]=[CH:22][C:13]=3[N:12]=2)[CH3:10])[C:3]=1[C:26]#[N:27]

Participants

7

Reactant 4

HCID 2906CyclopentylamineHCID 81531DiisopropylethylamineHCID 2724700Benzotriazol-1-yl-oxytripyrrolidinophosphoniumHCID 58459203HCID 58459203, compound

Product 1

HCID 58459108HCID 58459108, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of crude (S)-2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-1-cyclopropyl-1H-benzo[d]imidazole-7-carboxylic acid (132 mg, 0.36 mmol) in DMF (3 mL) was added cyclopentanamine (0.10 mL, 1.0 mmol), N-ethyl-N-isopropylpropan-2-amine (0.060 mL, 0.36 mmol) and 1 h-benzotriazol-1-yl-oxytripyrrolidinophosphonium (190 mg, 0.36 mmol). The resulting mixture was stirred at rt for 2 h. The reaction mixture was diluted with EtOAc, washed with water, brine, dried over magnesium sulfate, and concentrated in vacuo. Purification of the residue by flash chromatography over silica gel, using 0 to 10% gradient of MeOH in DCM-EtOAc (1:1) with 0.2% NH4OH as eluent gave 2-((1S)-1-((6-amino-5-cyano-4-pyrimidinyl)amino)ethyl)-N-cyclopentyl-1-cyclopropyl-1H-benzimidazole-7-carboxamide: 1H NMR (400 MHz, MeOH-d4) δ 8.03 (1H, s), 7.70 (1H, d, J=8.0 Hz), 7.37 (1H, d, J=8.0 Hz), 7.28 (1H, t, J=8.0 Hz), 6.03 (1H, q, J=8.0 Hz), 4.45-4.38 (1H, m), 4.11 (1H, dd, J=8.0, 4.0 Hz), 3.53-3.44 (1H, m), 2.15-2.05 (2H, m), 1.88-1.78 (2H, m), 1.75-1.60 (4H, m), 1.38-1.10 (3H, m), 1.00-0.92 (1H, m); LC-MS (ESI) m/z 431.2 [M+H]+.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by flash chromatography over silica gel

Sources & evidence

ORD record
ord-af320aaaedc541b98af7f199f1846611
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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