2-(dimethylamino)ethyl-2-(4-((1E,4E)-2-(tert-butoxycarbonylamino)-4-((3-(tert-butyldimethylsilyloxy)propyl)(propyl)carbamoyl)-3H-benzo[b]azepin-8-yl)phenyl)acetate → 2-(dimethylamino)ethyl-2-(4-((1E,4E)-2-amino-4-((3-hydroxypropyl)(propyl)carbamoyl)-3H-benzo[b]azepin-8-yl)phenyl)acetate

HRID 2364646Notes

Reaction equation

HRID 2364646 reaction equation
[CH3:1][N:2]([CH3:51])[CH2:3][CH2:4][O:5][C:6](=[O:50])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][C:17]3=[C:18]([CH:49]=2)[N:19]=[C:20]([NH:41]C(OC(C)(C)C)=O)[CH2:21][C:22]([C:24](=[O:40])[N:25]([CH2:29][CH2:30][CH2:31][O:32][Si](C(C)(C)C)(C)C)[CH2:26][CH2:27][CH3:28])=[CH:23]3)=[CH:10][CH:9]=1>ClCCl.C(O)(C(F)(F)F)=O>[CH3:51][N:2]([CH3:1])[CH2:3][CH2:4][O:5][C:6](=[O:50])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][C:17]3=[C:18]([CH:49]=2)[N:19]=[C:20]([NH2:41])[CH2:21][C:22]([C:24](=[O:40])[N:25]([CH2:29][CH2:30][CH2:31][OH:32])[CH2:26][CH2:27][CH3:28])=[CH:23]3)=[CH:12][CH:13]=1

Participants

4

Reactant 1

HCID 866526872-(dimethylamino)ethyl-2-(4-((1E,4E)-2-(tert-butoxycarbonylamino)-4-((3-(tert-butyldimethylsilyloxy)propyl)(propyl)carbamoyl)-3H-benzo[b]azepin-8-yl)phenyl)acetate

Product 1

HCID 509439572-(dimethylamino)ethyl-2-(4-((1E,4E)-2-amino-4-((3-hydroxypropyl)(propyl)carbamoyl)-3H-benzo[b]azepin-8-yl)phenyl)acetate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

2-(dimethylamino)ethyl-2-(4-((1E,4E)-2-(tert-butoxycarbonylamino)-4-((3-(tert-butyldimethylsilyloxy)propyl)(propyl)carbamoyl)-3H-benzo[b]azepin-8-yl)phenyl)acetate was dissolved in 2 mls of dichloromethane and 0.5 ml of TFA. After about one hour, the mixture was concentrated under reduced pressure and the resulting residue was then re-dissolved in dichloromethane and 1 ml of concentrated ammonium hydroxide added and the mixture vigorously stirred for 15 minutes. This mixture was then diluted with water, extracted with dichloromethane (2×), extracts dried over sodium sulfate and concentrated under reduced pressure. Preparative thin layer chromatography (2×0.5 mm plates, 10% MeOH/DCM/0.5% NH4OH) afforded 2-(dimethylamino)ethyl-2-(4-((1E,4E)-2-amino-4-((3-hydroxypropyl)(propyl)carbamoyl)-3H-benzo[b]azepin-8-yl)phenyl)acetate. 1H NMR (400 MHz, CDCl3) δ 7.59-7.64 (m, 2H), 7.48-7.51 (m, 1H), 7.28-7.38 (m, 4H), 6.87 (s, 1H), 4.19-4.24 (m, 2H), 3.58-3.74 (m, 6H), 3.44-3.52 (m, 2H), 2.84 (s, 2H), 2.54-2.61 (m, 2H), 2.27 (s, 6H), 1.79-1.86 (m, 2H), 1.65-1.76 (m, 2H), 0.89-0.97 (m, 3H); m/z (APCI-pos) M+1=507.2.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. dissolutionthe resulting residue was then re-dissolved in dichloromethane
  3. addition1 ml of concentrated ammonium hydroxide added
  4. additionThis mixture was then diluted with water
  5. extractionextracted with dichloromethane (2×)
  6. dry with materialextracts dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f71236ae846d44308f6f9b50f83080ab
Source dataset
uspto-grants-2014_04
Patent number
US08691809B2

Reaction notes

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