Hydrazine hydrate (1:1) → 4-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzoic acid hydrazide

HRID 8952Notes

Reaction equation

HRID 8952 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([CH2:22][C:23]2[NH:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[N:24]=2)[CH:12]2[C:21]3[N:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH2:15][CH2:14][CH2:13]2)=[CH:6][CH:5]=1.O.[NH2:34][NH2:35].C(=O)(O)[O-].[Na+]>C(O)C>[NH:24]1[C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[N:27]=[C:23]1[CH2:22][N:11]([CH2:10][C:7]1[CH:6]=[CH:5][C:4]([C:3]([NH:34][NH2:35])=[O:2])=[CH:9][CH:8]=1)[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 516892Sodium BicarbonateHCID 207256284-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzoic acid methyl ester

Product 1

HCID 207256204-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzoic acid hydrazideYield 63.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 4-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzoic acid methyl ester (AMD9711) (140 mg, 0.33 mmol) in dry ethanol (3 mL) was added hydrazine monohydrate (0.5 mL, 10.3 mmol) and the resulting mixture was heated at 80° C. for 24 h. Saturated aqueous sodium bicarbonate (5 mL) was added, the phases separated and the aqueous layer extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification of the crude material by radial chromatography (1 mm plate, 75:1:1 CH2Cl2—MeOH—NH4OH) afforded the title compound (89 mg, 61%) as a white solid. 1H NMR (CDCl3) δ 1.64–1.68 (m, 1H), 1.94–2.04 (m, 2H), 2.20–2.24 (m, 1H), 2.66–2.72 (m, 1H), 2.78–2.83 (m; 1H), 3.73 (s, 2H), 3.93 (d, 1H, J=16 Hz), 4.00–4.12 (m, 3H), 4.15 (d, 1H, J=16 Hz), 7.14–7.18 (m, 3H), 7.40 (d, 2H, J=8 Hz), 7.50 (br d, 1H, J=7 Hz), 7.58 (d, 2H, J=8 Hz), 7.62 (br d, 1H, J=7 Hz), 8.06 (s, 1H), 8.66 (dd, 1H, J=5, 1Hz); 13C NMR (CDCl3) δ 21.2, 23.6, 29.0, 48.7, 53.7, 60.4, 111.4, 118.4, 121.5, 122.3, 126.9, 128.6, 131.5, 134.7, 137.3, 143.5, 146.8, 155.8, 157.1, 168.4. ES-MS m/z 427 (M+H). Anal. Calcd. for C25H26N6O.0.5CH2Cl2: C, 65.31; H, 5.80; N, 17.92. Found: C, 65.22; H, 5.77; N, 17.97.

Workup

  1. customthe phases separated
  2. extractionthe aqueous layer extracted with CH2Cl2 (3×10 mL)
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude material by radial chromatography (1 mm plate, 75:1:1 CH2Cl2—MeOH—NH4OH)

Sources & evidence

ORD record
ord-b74f5706fcb7405d87133dc30ae3f25c
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Reaction notes

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