(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidine → HCID 10217083, compound

HRID 1072097Notes

Reaction equation

HRID 1072097 reaction equation
C1(S([CH2:9][C:10]2[CH:11]=[CH:12][N:13]3[C:18]=2[C:17]([NH:19][C:20]2[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=2)[N:25]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)[N:24]=[CH:23]4)=[N:16][CH:15]=[N:14]3)=O)C=CC=CC=1.C(OC([NH:44][C@@H:45]1[CH2:49][CH2:48][NH:47][CH2:46]1)=O)(C)(C)C>C(Cl)Cl>[NH2:44][C@@H:45]1[CH2:49][CH2:48][N:47]([CH2:9][C:10]2[CH:11]=[CH:12][N:13]3[C:18]=2[C:17]([NH:19][C:20]2[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=2)[N:25]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)[N:24]=[CH:23]4)=[N:16][CH:15]=[N:14]3)[CH2:46]1

Participants

4

Reactant 2

HCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 22390503HCID 22390503, compound

Product 1

HCID 10217083HCID 10217083, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of (5-benzenesulfinylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-amine (100 mg, 0.20 mmole) and (3R)-3-(N-tert-butoxycarbonylamino)pyrrolidine; (380 mg, 10 equiv) in a sealed tube was heated at 130° C. for 35 hr. The reaction mixture was taken up in DCM, washed water and dried (Na2SO4). After removal of the solvent the residue was taken up in DCM (1.5 mL) and TFA (1 mL) was added. The solvents were removed and the residue was dissolved in DCM, washed with water, and dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate employing gradient elution with DCM containing 1 to 5% MeOH) to afforded the title compound as an oil (13 mg, 14%). 1H NMR (CDCl3) δ 1.49 (br s, 2H), 1.66 (m, 1H), 2.29 (m, 1H), 2.43 (m, 1H), 3.69 (m, 1H), 3.87 (d, 1H, J=13.5 Hz), 3.96 (d, 1H, J=13.5 Hz), 5.58 (s, 2H), 6.49 (d, 1H, J=3 Hz), 6.8-7.6 (m, 7H), 7.92 (s, 1H), 8.04 (s, 1H), 8.26 (d, 1H, J=2 Hz); MS: 457 (M+H)+; HPLC Ret Time: 1.15 min (YMC Xterra ODS S7 C18, 3.0×50 mm column, 2 min gradient, 5 mL/min).

Workup

  1. washwashed water
  2. dry with materialdried (Na2SO4)
  3. customAfter removal of the solvent the residue
  4. additionTFA (1 mL) was added
  5. customThe solvents were removed
  6. dissolutionthe residue was dissolved in DCM
  7. washwashed with water
  8. dry with materialdried (Na2SO4)
  9. customRemoval of the solvent
  10. washfollowed by radial chromatography (2 mm silica gel plate employing gradient elution with DCM containing 1 to 5% MeOH)

Sources & evidence

ORD record
ord-393e13fc8ecb4605b7da08f7ed8b3b8b
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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