1,2-Dichloroethane → 3-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-isopropylcarbamoyl-benzylamino)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041544Notes

Reaction equation

HRID 2041544 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl.[C:28]([O:32][C:33]([N:35]1[CH2:41][CH2:40][C:39]2[C:42]([NH:47][CH2:48][C:49]3[CH:54]=[CH:53][C:52]([C:55](O)=[O:56])=[C:51]([F:58])[CH:50]=3)=[C:43]([Cl:46])[CH:44]=[CH:45][C:38]=2[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>C1COCC1>[C:28]([O:32][C:33]([N:35]1[CH2:41][CH2:40][C:39]2[C:42]([NH:47][CH2:48][C:49]3[CH:54]=[CH:53][C:52]([C:55](=[O:56])[NH:4][CH:1]([CH3:3])[CH3:2])=[C:51]([F:58])[CH:50]=3)=[C:43]([Cl:46])[CH:44]=[CH:45][C:38]=2[CH2:37][CH2:36]1)=[O:34])([CH3:30])([CH3:31])[CH3:29]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 6363IsopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57656039HCID 57656039, compound

Product 1

HCID 576564403-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-isopropylcarbamoyl-benzylamino)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add isopropylamine (0.15 mL, 1.8 mmol), HOBT (0.24 g, 1.8 mmol), diisopropylethylamine (0.63 mL, 3.6 mmol) and EDC (0.34 g, 1.8 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 (0.403 g, 0.9 mmol) in anhydrous THF (11.8 mL) at room temperature. Stir overnight at room temperature and partition the mixture between EtOAc (250 mL) and saturated aqueous NaHCO3 (100 mL). Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (40 g RediSep® column) eluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 50 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-isopropylcarbamoyl-benzylamino)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a thick colorless oil (0.439 g, 100%). MS (ES+) m/z: 490.2 (M+H)+.

Workup

  1. custompartition the mixture between EtOAc (250 mL) and saturated aqueous NaHCO3 (100 mL)
  2. dry with materialDry the organic phase over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate in vacuo
  5. customPurify by chromatography on silica gel (40 g RediSep® column)
  6. washeluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 50 mL/min)

Sources & evidence

ORD record
ord-b313b4d870f446a9a8636e71c3c235f3
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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