Ammonia → HCID 51033411, compound

HRID 37992Notes

Reaction equation

HRID 37992 reaction equation
[N:1]1([C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:15]=[CH:16][C:17]4[CH:23]=[CH:22][CH2:21][C:20](NC(=O)[O-])=[N:19][C:18]=4[CH:28]=3)=[CH:10][CH:9]=2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:29](O)([C:31](F)(F)F)=[O:30].[NH3:36].[CH3:37][OH:38]>C(Cl)Cl>[NH2:36][C:20]1[CH2:21][C:22]([C:37]([N:1]([CH2:5][CH2:31][CH2:29][OH:30])[CH2:2][CH2:3][CH3:4])=[O:38])=[CH:23][C:17]2[CH:16]=[CH:15][C:14]([C:11]3[CH:12]=[CH:13][C:8]([C:6]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[O:7])=[CH:9][CH:10]=3)=[CH:28][C:18]=2[N:19]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 6422Trifluoroacetic acidHCID 86653473HCID 86653473, compound

Product 1

HCID 51033411HCID 51033411, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl (1E,4E)-4-(3-(tert-butyldimethylsilyloxy)propyl)(propyl)carbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate (459 mg, 0.37 mmol) in CH2Cl2 (4 mL) at 0° C. was added TFA (1.00 mL). The resulting mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to give the crude material that was azeotroped with toluene-EtOH (3 mL/1 mL) twice. The crude material was dried under reduced pressure for 30 min. The crude material was dissolved into CH2Cl2 (˜3 mL) again and treated with NH3 in MeOH (0.30 mL, 2.1 mmol, 7 N solution in MeOH) at room temperature. The resulting mixture was stirred for 1 h. The resulting mixture was concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (3 to 7% MeOH in CH2Cl2, gradient) to afford 105 mg (59%) of (1E,4E)-2-amino-N-(3-hydroxypropyl)-N-propyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxamide. MS APCI (+) m/z 475 detected; 1H-NMR (400 MHz, CDCl3) δ 7.67 (d, 2H), 7.60 (d, 2H), 7.51 (br s, 1H), 7.30-7.37 (m, 2H), 6.88 (s, 1H), 3.60-3.69 (m, 6H), 3.48-3.52 (m, 4H), 2.83 (s, 2H), 1.82-2.00 (m, 6H), 1.68-1.74 (m, 2H), 0.93 (t, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give the crude material that
  3. customwas azeotroped with toluene-EtOH (3 mL/1 mL) twice
  4. dry with materialThe crude material was dried under reduced pressure for 30 min
  5. dissolutionThe crude material was dissolved into CH2Cl2 (˜3 mL) again
  6. stirringThe resulting mixture was stirred for 1 h
  7. concentrationThe resulting mixture was concentrated under reduced pressure
  8. customto give the crude material that
  9. customwas purified by silica gel flash column chromatography (3 to 7% MeOH in CH2Cl2, gradient)

Sources & evidence

ORD record
ord-46ed76d2821a40f2971b59b69bac8531
Source dataset
uspto-grants-2013_09
Patent number
US08524702B2

Reaction notes

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