Trifluoroacetic acid → HCID 90424043, compound

HRID 1055173Notes

Reaction equation

HRID 1055173 reaction equation
FC(F)(F)C(O)=O.[N:8]1[CH:9]=[CH:10][N:11]2[CH2:16][CH:15]([O:17][CH2:18][C:19]([O-:21])=O)[CH2:14][CH2:13][C:12]=12.C(N(CC)CC)C.O.Cl.Cl.[CH2:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH:33]1[NH:41][C:42]1[N:43]=[CH:44][C:45]2[CH2:50][NH:49][CH2:48][C:46]=2[N:47]=1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl.CN(C)C=O>[CH2:34]1[C:35]2[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:32][CH:33]1[NH:41][C:42]1[N:43]=[CH:44][C:45]2[CH2:50][N:49]([C:19](=[O:21])[CH2:18][O:17][CH:15]3[CH2:16][N:11]4[CH:10]=[CH:9][N:8]=[C:12]4[CH2:13][CH2:14]3)[CH2:48][C:46]=2[N:47]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 86726534N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrateHCID 131736344HCID 131736344, compound

Product 1

HCID 90424043HCID 90424043, compoundYield 33.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Add trifluoroacetic acid (3 mL) to a flask containing tert-butyl 2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yloxylacetate (0.30 g; 2.04 equiv; 1.19 mmoles) in dichloromethane (3 mL), and stir at ambient temperature for 1 hour. Concentrate the mixture, add toluene (2×5 mL), and reconcentrate (2×). Add methanol (10 mL) followed by 5 N hydrochloric acid (1 mL), then concentrate. Add toluene (4×5 mL) and reconcentrate (4×). Add dimethylformamide (5 mL), triethylamine (15 equiv; 8.74 mmol; 1.22 mL), N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrate (0.20 g; 1.0 equiv; 0.583 mmoles) and 1-propanephosphonic acid cyclic anhydride (0.70 mL; 2.0 equiv; 1.17 mmoles) and stir at ambient temperature for 2 hours. Load the solution directly onto a silica gel column and purify by column chromatography (hexanes to ethyl acetate to 20% methanol in ethyl acetate) to give impure product. Further purify the crude product by reverse phase chromatography to afford 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yloxy)ethanone (0.083 g; 33%) as a light yellow foam. MS (m/z): 431(M+1).

Workup

  1. concentrationConcentrate the mixture
  2. additionadd toluene (2×5 mL), and reconcentrate (2×)
  3. concentrationconcentrate
  4. customLoad the solution directly onto a silica gel column and purify by column chromatography (hexanes to ethyl acetate to 20% methanol in ethyl acetate)
  5. customto give impure product
  6. customFurther purify the crude product by reverse phase chromatography

Sources & evidence

ORD record
ord-caa05d19dc3b4995bfc3add32f7f1b6f
Source dataset
uspto-grants-2016_07
Patent number
US09394317B2

Reaction notes

Loading…