Cyclopentyl Isocyanate → HCID 68928323, compound

HRID 860722Notes

Reaction equation

HRID 860722 reaction equation
OC(C(F)(F)F)=O.C1([C:14]2[C:15]3[CH:16]=[CH:17][C:18]([C:32]([O:34]C)=[O:33])=[CH:19][C:20]=3[N:21]3[C:27]=2[C:26]2[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=2[NH:24][CH2:23][CH2:22]3)CCCCC1.C1(N=C=O)CCCC1>C(N(CC)CC)C.C(Cl)Cl>[CH:28]1[C:26]2[C:27]3[N:21]([C:20]4[CH:19]=[C:18]([C:32]([OH:34])=[O:33])[CH:17]=[CH:16][C:15]=4[CH:14]=3)[CH:22]=[CH:23][NH:24][C:25]=2[CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 643500Cyclopentyl IsocyanateHCID 131726178HCID 131726178, compound

Product 1

HCID 68928323HCID 68928323, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of methyl (13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)-carboxylate TFA (80 mg, 0.17 mmol) in triethylamine (0.20 mL) and CH2Cl2 (5 mL) which had been stirred for 5 min. was added cyclopentyl isocyanate (0.20 mL, 1.77 mmol). The reaction solution was stirred overnight at rt, concentrated to dryness, dissolved into MeOH/THF (1:1, 3 mL) and treated with 1M aqueous NaOH (0.80 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min in a sealed tube. The clear solution was diluted with H2O (3 mL), neutralized with 1M aqueous HCl (0.80 mL) and concentrated to remove organic solvents. The solids were collected by filtration, washed with water and purified by preparative HPLC (MeOH/H2O with NH4OAc buffer) to yield 5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylic acid, 13-cyclohexyl-5-[(cyclopentylamino)carbonyl]-6,7-dihydro (8 mg, 0.02 mmol, 10%) as an off-white solid. 1HNMR (300 MHz, CD3OD) δ 8.14 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.72 (dd, J=8.4, 1.1 Hz, 1H), 7.68–7.59 (m, 3H), 7.52–7.46 (m, 1H), 4.79–4.60 (m, 2H), 4.05–3.46 (m, 3H), 3.06–2.92 (m, 1H), 2.14–1.25 (m, 18H). LCMS: m/e 472 (M+H)+, ret time 2.66 min, column A, 3 minute gradient.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutiondissolved into MeOH/THF (1:1, 3 mL)
  3. additiontreated with 1M aqueous NaOH (0.80 mL)
  4. stirringThe reaction mixture was stirred
  5. temperatureheated at 80° C. with microwave irradiation for 15 min in a sealed tube
  6. additionThe clear solution was diluted with H2O (3 mL)
  7. concentrationconcentrated
  8. customto remove organic solvents
  9. filtrationThe solids were collected by filtration
  10. washwashed with water
  11. custompurified by preparative HPLC (MeOH/H2O with NH4OAc buffer)

Sources & evidence

ORD record
ord-8281d9f8008c4f7eb3bf63015d32990a
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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