Ammonia → HCID 69204947, compound

HRID 860738Notes

Reaction equation

HRID 860738 reaction equation
N.[C:2]([O:6][C:7]([C:9]1([C:14]([OH:16])=O)[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].C[N:18](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CS(C)=O>[C:2]([O:6][C:7]([C:9]1([C:14]([NH2:18])=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 69207214HCID 69207214, compound

Product 1

HCID 69204947HCID 69204947, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 2 M methanolic ammonia (3.3 mL) was added to a stirred solution of 1-(tert-butoxycarbonyl)cyclopentanecarboxylic acid (1.0 g, 4.36 mmol), TEA (3.65 mL, 0.0262 mol), and TBTU (1.61 g, 5 mmol) in DMSO (5 mL) at 22° C. After stirring for 1 hr the solution was poured into ice cold water. The mixture was extracted with ethyl acetate. The extract was washed with brine (2×), dried over MgSO4 and concentrated to leave a colorless solid. Recrystallization from ethyl acetate-hexanes afforded 1-(tert-butoxycarbonyl)cyclopentanecarboxamide (660 mg, 66%). TFA (2.5 mL) was added to a stirred solution of the amide (445 g) in methylene chloride (2.5 mL). The solution was stirred for 1 hr at 22° C. and then concentrated to an oil. Trituration with diethyl ether afforded the TFA salt of 1-aminocyclopentanecarboxamide as a colorless solid. Coupling of the amine with, 13-cyclohexyl-6,7-dihydro-6-oxo-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylic acid afforded the titled compound. MS m/z 486 (MH+); 1H NMR (300 MHz, DMSO-D6) δ ppm 1.09–2.29 (m, 8 H) 2.42–2.56 (m, 2 H) 2.86 (s, 1 H) 4.61 (s, 1 H) 4.97–5.17 (m, 1 H) 6.73 (s, 1 H) 7.03 (s, 1 H) 7.29 (d, J=7.68 Hz, 1 H) 7.38 (t, J=7.50 Hz, 1 H) 7.50 (t, J=7.50 Hz, 2 H) 7.61 (d, J=9.51 Hz, 1 H) 7.88 (d, J=8.78 Hz, 1 H) 8.28 (s, 1 H).

Workup

  1. additionwas poured into ice cold water
  2. extractionThe mixture was extracted with ethyl acetate
  3. washThe extract was washed with brine (2×)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto leave a colorless solid
  7. customRecrystallization from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-057f62ffd4e2416f8e1d9dd8b3e1f083
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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