1,2-Dichloroethane → HCID 68412326, compound

HRID 1879986Notes

Reaction equation

HRID 1879986 reaction equation
C(Cl)C[Cl:3].[N:5]1[C:10]2[NH:11][CH2:12][CH2:13][CH2:14][O:15][C:9]=2[CH:8]=[C:7]([CH:16]=[CH:17][C:18]([OH:20])=O)[CH:6]=1.[CH3:21][NH:22][CH2:23][C:24]1[O:25][C:26]2[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]=1[CH3:29].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O>[ClH:3].[CH3:21][N:22]([CH2:23][C:24]1[O:25][C:26]2[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]=1[CH3:29])[C:18](=[O:20])[CH:17]=[CH:16][C:7]1[CH:6]=[N:5][C:10]2[NH:11][CH2:12][CH2:13][CH2:14][O:15][C:9]=2[CH:8]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 46785639N-methyl-1-(3-methylbenzofuran-2-yl)methanamineHCID 68412387HCID 68412387, compound

Product 1

HCID 68412326HCID 68412326, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

EDC (108 mg, 0.56 mmol) was added to a solution of 3-(6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocyclohepten-3-yl)-acrylic acid (95 mg, 0.43 mmol), methyl-(3-methyl-benzofuran-2-ylmethyl)-amine (100 μL, 0.52 mmol), HOBt.H2O (64 mg, 0.47 mmol) and DIPEA (225 μL, 1.29 mmol) in dry DMF (4 mL). After stirring for 23 hr, the mixture was cooled (10° C.) and treated with water (50 mL). The precipitated crude product was separated by decantation and purified by chromatography (silica, EtOAc). The clean fractions of the free base were collected, concentrated to 10 mL and treated with HCl (0.7 mL, 1.4 mmol, 2M in Et2O). The resulting precipitate was collected by filtration, washed with EtOAc and hexanes to afford the title compound (123 mg, 57%). 1H NMR (300 MHz, DMSO-d6, 8): 8.07 (m, 2H), 7.58-7.41 (m, 3H), 7.36-7.15 (m, 3H), 4.99 and 4.77 (rotamers, 2s, 2H), 4.28 (m, 2H), 3.57 (m, 2H), 3.16 and 2.90 (rotamers, 2s, 3H), 2.25 (s, 3H), 2.11 (m, 2H). MS (ESI): m/e 378 (M+H)+.

Workup

  1. customThe precipitated crude product
  2. customwas separated by decantation
  3. custompurified by chromatography (silica, EtOAc)
  4. customThe clean fractions of the free base were collected
  5. concentrationconcentrated to 10 mL
  6. filtrationThe resulting precipitate was collected by filtration
  7. washwashed with EtOAc and hexanes

Sources & evidence

ORD record
ord-2d0f14a9a7a7437c80ea0a5101492640
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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