Ammonia → HCID 51033411, compound

HRID 593433Notes

Reaction equation

HRID 593433 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][N:12]([CH2:47][CH2:48][CH3:49])[C:13]([C:15]1=[CH:16][C:17]2[CH:33]=[CH:32][C:31]([C:34]3[CH:39]=[CH:38][C:37]([C:40]([N:42]4[CH2:46][CH2:45][CH2:44][CH2:43]4)=[O:41])=[CH:36][CH:35]=3)=[CH:30][C:18]=2[N:19]=[C:20]([NH:22]C(=O)OC(C)(C)C)[CH2:21]1)=[O:14])(C(C)(C)C)(C)C.C(O)(C(F)(F)F)=O.N.CO>C(Cl)Cl>[NH2:22][C:20]1[CH2:21][C:15]([C:13]([N:12]([CH2:11][CH2:10][CH2:9][OH:8])[CH2:47][CH2:48][CH3:49])=[O:14])=[CH:16][C:17]2[CH:33]=[CH:32][C:31]([C:34]3[CH:35]=[CH:36][C:37]([C:40]([N:42]4[CH2:46][CH2:45][CH2:44][CH2:43]4)=[O:41])=[CH:38][CH:39]=3)=[CH:30][C:18]=2[N:19]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 6422Trifluoroacetic acidHCID 86653471tert-butyl (1E,4E)-4-((3-(tert-butyldimethylsilyloxy)propyl)(propyl)carbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate

Product 1

HCID 51033411HCID 51033411, compoundYield 59.8%

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-3cd7fec383d74a0684c0ef6291e8173a
Source dataset
uspto-grants-2016_01
Patent number
US09242964B2

Reaction notes

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