Trifluoroacetic acid → HCID 67492183, compound

HRID 1945938Notes

Reaction equation

HRID 1945938 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:20][C@@H:19]2[CH2:21][C@H:16]1[CH2:17][N:18]2[CH2:22][C:23]1[N:24]([CH3:49])[C:25]2[C:30]([N:31]=1)=[C:29]([N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)[N:28]=[C:27]([N:38]1[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[N:40]=[C:39]1[CH2:47][CH3:48])[N:26]=2)=O)(C)(C)C>C(Cl)Cl>[C@H:19]12[CH2:21][C@H:16]([NH:15][CH2:20]1)[CH2:17][N:18]2[CH2:22][C:23]1[N:24]([CH3:49])[C:25]2[C:30]([N:31]=1)=[C:29]([N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)[N:28]=[C:27]([N:38]1[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[N:40]=[C:39]1[CH2:47][CH3:48])[N:26]=2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67492611HCID 67492611, compound

Product 1

HCID 67492183HCID 67492183, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (200 mg, 0.51 mmol), (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (122 mg, 0.62 mmol) and molecular sieves (4 Å, powdered, 520 mg) in DCE (10 mL) was stirred at ambient temperature for 3 h. Sodium triacetoxyborohydride (162 mg, 0.76 mmol) was added and the mixture stirred for 17 h, then loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, EtOAc:MeOH; gradient from 100:0 to 85:15) to give (1S,4S)-5-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester as a white solid. TFA (3 mL) was added to a solution of (1S,4S)-5-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester in DCM (10 mL) and the mixture stirred at ambient temperature for 30 min, then loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; gradient from 100:0 to 85:15) to afford 395 as a white solid (153 mg, 63%). LCMS (Method G): RT=5.78 min, M+H+=474. 1H NMR (CDCl3, 400 MHz) δ 8.01 (m, 1 H); 7.75 (m, 1 H); 7.26 (m, 2 H); 4.34 (m, 4 H); 4.00 (d, J=13.6 Hz, 1 H); 3.92-3.83 (m, 8 H); 3.70 (s, 1 H); 3.45 (s, 1 H); 3.35 (q, J=7.5 Hz, 2 H); 3.25 (d, J=10.2 Hz, 1 H); 2.97-2.91 (m, 2 H); 2.70 (d, J=10.2 Hz, 1 H); 1.85 (d, J=10.1 Hz, 1 H); 1.70 (d, J=10.1 Hz, 1 H) and 1.45 (t, J=7.5 Hz, 3 H)

Workup

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. customThe product was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; gradient from 100:0 to 85:15)

Sources & evidence

ORD record
ord-1b487d2b99324df98c7c8fb1e605ab44
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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