Diisopropylethylamine → HCID 71197908, compound

HRID 2415542Notes

Reaction equation

HRID 2415542 reaction equation
C(N(CC)C(C)C)(C)C.Cl.[C:11]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C@H:17](C(O)=O)[CH2:16]1)([CH3:14])([CH3:13])[CH3:12].Cl.[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([C:44]2[CH2:45][CH2:46][NH:47][CH2:48][CH:49]=2)=[C:37]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH:38]=1.F[P-](F)(F)(F)(F)F.N1([O:66][C:67](N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.ON1C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:11]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C@H:17]([C:67]([N:47]2[CH2:46][CH:45]=[C:44]([C:36]3[CH:35]=[CH:34][C:33]([Cl:32])=[CH:38][C:37]=3[CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH2:49][CH2:48]2)=[O:66])[CH2:16]1)([CH3:12])([CH3:14])[CH3:13]

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67212109(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochlorideHCID 86590371HCID 86590371, compound

Product 1

HCID 71197908HCID 71197908, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N-diisopropylethylamine (1.36 mL, 7.80 mmol) was added to a stirred suspension of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (1-7) (0.831 g, 2.60 mmol), methyl [5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]acetate hydrochloride (1-6) (0.690 g, 2.60 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.19 g, 3.12 mmol) and 1-hydroxy-7-azabenzotriazole (0.425 g, 3.12 mmol) in N,N-dimethylformamide (5.2 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The combined organic extracts were washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent) provided 1-8 as a pale yellow oil (m/z (ES) 531 (MH+).

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent)

Sources & evidence

ORD record
ord-d907e828abaa47ddb437d0fe469e85ac
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Reaction notes

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