Cyclohexanol → HCID 75201791, compound

HRID 1746119Notes

Reaction equation

HRID 1746119 reaction equation
[CH3:1][N:2]1[C:10]([CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[N:9][C:8]2[CH:7]=[C:6]([N:17]([CH2:21][CH2:22][Cl:23])[CH2:18][CH2:19][Cl:20])[CH:5]=[CH:4][C:3]1=2.Cl.[CH:25]1(O)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C1C=CN=CC=1)C>[CH:25]1([O:15][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][C:10]2[N:2]([CH3:1])[C:3]3[CH:4]=[CH:5][C:6]([N:17]([CH2:18][CH2:19][Cl:20])[CH2:21][CH2:22][Cl:23])=[CH:7][C:8]=3[N:9]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 7966Cyclohexanol2×HCID 10868Dicyclohexylcarbodiimide2×HCID 77082Bendamustine Hydrochloride

Product 1

HCID 75201791HCID 75201791, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst2×

Procedure

A 250 mL three neck round bottom flask was equipped with an overhead stirrer, thermocouple, temperature controller and nitrogen sweep then charged with 10 g (25.34 mmol) of bendamustine hydrochloride, 2.56 g (2.7 mL, 25.6 mmol, 1.01 eq) of cyclohexanol, 5.3 g (25.6 mmol, 1.01 eq) of dicyclohexylcarbodiimide (DCC), 100 mL of MDC and 0.31 g (2.54 mmol, 0.1 eq) of DMAP. The reaction slurry was stirred at RT for 18 h until an in process analysis indicated the reaction was complete. Two new major product peaks were observed. Solids were removed by vacuum filtration and washed with 5 mL of MDC. The filtrate was washed with 4% aqueous sodium bicarbonate solution (2×100 mL) before drying over sodium sulfate, filtering and concentrating to dryness in vacuo to yield a yellow oil with some solids present. 1H NMR analysis indicated residual DMAP and cyclohexanol was along with DCC by-products were present in addition to the desired product. The residue was slurried with 50 mL of MDC to remove residual cyclohexanol then concentrated in vacuo and chromatographed. The chromatography was carried out using 50 g of silica gel 60, 230-400 mesh, eluting with 1:1 heptane/EtOAc collecting 100 mL fractions. Product containing fractions were combined and concentrated to dryness in vacuo to yield 3.11 g (7.06 mmol, 27.9%) of the product as an off-white solid with an HPLC purity of 97.8A %. 1H NMR (400 MHz, DMSO-d6) δ 7.31 (d, J=8.76 Hz, 1H), 6.93 (d, J=2.28 Hz, 1H), 6.77 (dd, J=2.40, 8.80 Hz, 1H), 4.65 (m, 1H), 3.7 (s, 8H), 3.65 (s, 3H), 2.83 (t, J=7.4 Hz, 2H), 2.44 (t, J=7.36 Hz, 2H), 2.00 (m, 2H), 1.76 (m, 4H), 1.65 (m, 2H), 1.33 (m, b, 6H).

Workup

  1. customSolids were removed by vacuum filtration
  2. washwashed with 5 mL of MDC
  3. washThe filtrate was washed with 4% aqueous sodium bicarbonate solution (2×100 mL)
  4. dry with materialbefore drying over sodium sulfate
  5. filtrationfiltering
  6. concentrationconcentrating to dryness in vacuo
  7. customto yield a yellow oil with some solids present

Sources & evidence

ORD record
ord-03045fd37553494d88a452f7d1d5a266
Source dataset
uspto-grants-2015_10
Patent number
US09149464B2

Reaction notes

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