1,2-Dichloroethane → HCID 57655943, compound

HRID 911684Notes

Reaction equation

HRID 911684 reaction equation
[CH2:1]([NH2:4])[CH2:2][CH3:3].C1C=CC2N(O)N=NC=2C=1.C(NC(C)C)(C)C.C(Cl)CCl.[C:26]([O:30][C:31]([N:33]1[CH2:39][CH2:38][C:37]2[C:40]([NH:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([C:53](O)=[O:54])=[C:49]([F:56])[CH:48]=3)=[C:41]([Cl:44])[CH:42]=[CH:43][C:36]=2[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>C1COCC1>[C:26]([O:30][C:31]([N:33]1[CH2:39][CH2:38][C:37]2[C:40]([NH:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([C:53](=[O:54])[NH:4][CH2:1][CH2:2][CH3:3])=[C:49]([F:56])[CH:48]=3)=[C:41]([Cl:44])[CH:42]=[CH:43][C:36]=2[CH2:35][CH2:34]1)=[O:32])([CH3:28])([CH3:27])[CH3:29]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 7852PropylamineHCID 7912DiisopropylamineHCID 757711-HydroxybenzotriazoleHCID 57656039HCID 57656039, compound

Product 1

HCID 57655943HCID 57655943, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Add a solution of n-propylamine (6.3 mg, 0.11 mmol) in anhydrous THF (0.5 mL), HOBT (14.5 mg, 0.11 mmol), a solution of diisopropylamine (27.7 mg, 0.21 mmol) in anhydrous THF (0.5 mL) and EDC (20.5 mg, 6.11 mmol) to a mixture of 3-tert-butoxycarbonyl-6-(4-carboxy-3-fluoro-benzylamino)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (48.1 mg, 0.11 mmol) in anhydrous THF (1.4 mL) at room temperature. Stir overnight at room temperature and partition the mixture between EtOAc (50 mL) and saturated aqueous NaHCO3 (20 mL). Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (12 g RediSep® column) eluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-propylcarbamoyl-benzylamino)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a thick colorless oil (37.1 mg, 71%). MS (ES+) m/z: 490.2 (M+H)+.

Workup

  1. custompartition the mixture between EtOAc (50 mL) and saturated aqueous NaHCO3 (20 mL)
  2. dry with materialDry the organic phase over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate in vacuo
  5. customPurify by chromatography on silica gel (12 g RediSep® column)
  6. washeluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 35 mL/min)

Sources & evidence

ORD record
ord-91d9009a5f04426a9450b3a02e955c45
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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