Methylamine → (2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylate

HRID 908436Notes

Reaction equation

HRID 908436 reaction equation
F[B-](F)(F)F.[N:6]1([O+]=C(N(C)C)N(C)C)[C:10]2C=CC=CC=2N=N1.CN.[NH2:25][C:26]1[N:31]=[CH:30][C:29]([C:32]2[CH:33]=[N:34][N:35]([C@H:37]3[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:39]([C:49](O)=[O:50])[CH2:38]3)[CH:36]=2)=[CH:28][C:27]=1[C:52]1[O:53][C:54]2[CH:60]=[CH:59][CH:58]=[CH:57][C:55]=2[N:56]=1.C(N(CC)CC)C>CN(C=O)C>[NH2:25][C:26]1[N:31]=[CH:30][C:29]([C:32]2[CH:33]=[N:34][N:35]([C@H:37]3[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:47])([CH3:48])[CH3:46])=[O:43])[C@H:39]([C:49](=[O:50])[NH:6][CH3:10])[CH2:38]3)[CH:36]=2)=[CH:28][C:27]=1[C:52]1[O:53][C:54]2[CH:60]=[CH:59][CH:58]=[CH:57][C:55]=2[N:56]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 67389021(2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acidHCID 178484680HCID 178484680, compound

Product 1

HCID 67388909(2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylateYield 33.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A slurry of benzotriazol-1-yl-[bis(dimethylamino)methylene]oxonium tetrafluoroborate (149 mg) was added to methylamine (0.892 ml, 2M in methanol) and (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acid (175 mg) and triethylamine (0.883 ml) dissolved in DMF (8 ml) over a period of 10 minutes. The resulting solution was stirred at 25° C. overnight. The mixture was evaporated and a saturated solution of NaHCO3 (50 ml) was added to the mixture, extracted with methylene chloride (50 ml×2), dried over Magnesium sulphate, filtered and evaporated in reduce pressure. The reaction mixture was purified by preparative HPLC using a Waters X-Terra reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford (2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylate (60 mg) as a solid. Retention time: 3.44 min Mass spectrum: M+H+ 504

Workup

  1. customThe mixture was evaporated
  2. additiona saturated solution of NaHCO3 (50 ml) was added to the mixture
  3. extractionextracted with methylene chloride (50 ml×2)
  4. dry with materialdried over Magnesium sulphate
  5. filtrationfiltered
  6. customevaporated in reduce pressure
  7. customThe reaction mixture was purified by preparative HPLC
  8. additionThe fractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-49a18fa8279b44b59e1d8d47af9d3c15
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

Loading…