Trifluoroacetic acid → 4-amino-N-(1-(4-chlorophenyl)-3-ureidopropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

HRID 423020Notes

Reaction equation

HRID 423020 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:22][C:23]([C:25]2([NH:40]C(=O)OC(C)(C)C)[CH2:30][CH2:29][N:28]([C:31]3[C:32]4[CH:39]=[CH:38][NH:37][C:33]=4[N:34]=[CH:35][N:36]=3)[CH2:27][CH2:26]2)=[O:24])[CH2:16][CH2:17][NH:18][C:19]([NH2:21])=[O:20])=[CH:11][CH:10]=1>>[NH2:40][C:25]1([C:23]([NH:22][CH:15]([C:12]2[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=2)[CH2:16][CH2:17][NH:18][C:19]([NH2:21])=[O:20])=[O:24])[CH2:30][CH2:29][N:28]([C:31]2[C:32]3[CH:39]=[CH:38][NH:37][C:33]=3[N:34]=[CH:35][N:36]=2)[CH2:27][CH2:26]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57750390tert-butyl 4-(1-(4-chlorophenyl)-3-ureidopropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2×

Product 1

HCID 577503684-amino-N-(1-(4-chlorophenyl)-3-ureidopropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideYield 5.6%

Conditions

Temperature
20 °C

Procedure

TFA (3 mL) was added to tert-butyl 4-(1-(4-chlorophenyl)-3-ureidopropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 112) (379 mg, 0.66 mmol). The reaction was left to stir at 20° C. for 4 hours and then vacuumed to dryness. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 0.35M NH3/MeOH and pure fractions were evaporated to dryness to afford crude material. 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 to afford 4-amino-N-(1-(4-chlorophenyl)-3-ureidopropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (14.00 mg, 5.60%) as a white solid.

Workup

  1. waitThe reaction was left
  2. customThe crude product was purified by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. customwere evaporated to dryness
  5. customto afford crude material
  6. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-9a29302341054ca89971c46b50fbe78f
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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