1-Hydroxybenzotriazole → HCID 68571184, compound

HRID 1096856Notes

Reaction equation

HRID 1096856 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[O:28][CH:29]=[C:30]([CH2:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[N:31]=3)=[C:13]2[C:24](O)=[O:25])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:43]1([NH:46][CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=2[Cl:55])[CH2:45][CH2:44]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[O:28][CH:29]=[C:30]([CH2:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[N:31]=3)=[C:13]2[C:24](=[O:25])[N:46]([CH:43]2[CH2:44][CH2:45]2)[CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=2[Cl:55])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 834599Cyclopropyl-(2,3-dichloro-benzyl)-amine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride3×HCID 68572249HCID 68572249, compound

Product 1

HCID 68571184HCID 68571184, compoundYield 65.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a sol. of compound D5 (10 g, 14.7 mmol) in CH2Cl2 (200 mL) was added cyclopropyl-(2,3-dichlorobenzyl)amine (prepared by reductive amination from 2,3-dichlorobenzaldehyde and cyclopropylamine, 7.95 g, 36.8 mmol), DIPEA (10.1 mL, 58.8 mmol), DMAP (449 mg, 3.68 mmol), HOBt (2.48 g, 18.4 mmol), and EDC.HCl (8.45 g, 44.1 mmol). This mixture was stirred at rt for 3 days. EDC.HCl (2.83 g, 14.7 mmol) and DIPEA (2.5 mL, 26 mmol) were added, and the reaction mixture was stirred at rt for 24 h. EDC.HCl (2.82 g, 14.7 mmol) and cyclopropyl-(2,3-dichlorobenzyl)amine (3.10 g, 14.7 mmol) were added, and the mixture and was stirred for 48 h. CH2Cl2 was added, and the organic layer was washed with aq. 1M HCl (3×), and with aq. sat. NaHCO3 (1×). The org. layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:5→2:3) yielded the title compound (7.72 g, 65%). LC-MS: tR=1.31 min; ES+: 802.52.

Workup

  1. stirringthe reaction mixture was stirred at rt for 24 h
  2. stirringthe mixture and was stirred for 48 h
  3. washthe organic layer was washed with aq. 1M HCl (3×)
  4. dry with materiallayer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by FC (EtOAc/heptane 1:5→2:3)

Sources & evidence

ORD record
ord-fb90ef7f667f4e73b3ffa3510ea663c4
Source dataset
uspto-grants-2012_03
Patent number
US08138340B2

Reaction notes

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