Trifluoroacetic acid → HCID 42602173, compound

HRID 422979Notes

Reaction equation

HRID 422979 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][CH:10]([NH:18][C:19]([C:21]1([NH:36]C(=O)OC(C)(C)C)[CH2:26][CH2:25][N:24]([C:27]2[C:28]3[CH:35]=[CH:34][NH:33][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:23][CH2:22]1)=[O:20])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1>C(Cl)Cl>[NH2:36][C:21]1([C:19]([NH:18][CH:10]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[CH2:9][NH2:8])=[O:20])[CH2:22][CH2:23][N:24]([C:27]2[C:28]3[CH:35]=[CH:34][NH:33][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:25][CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57750411HCID 57750411, compound2×

Product 1

HCID 42602173HCID 42602173, compoundYield 11.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Trifluoroacetic acid (3 mL) was added to tert-butyl 4-(2-amino-1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 6) (0.514 g) in DCM (100 mL) at 25° C. The resulting solution was stirred at 25° C. for 3 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness. This material was then further purified by flash silica chromatography, elution gradient 0 to 10% methanolic ammonia (7N) in DCM. Pure fractions were evaporated to dryness to afford 4-amino-N-(2-amino-1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide as a colourless gum (0.047 g, 11.4%).

Workup

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customwere evaporated to dryness
  4. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness
  7. customThis material was then further purified by flash silica chromatography, elution gradient 0 to 10% methanolic ammonia (7N) in DCM
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-26c3190c82cb4c4cb7266b8316375eba
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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