Hydrochloric Acid → (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

HRID 423008Notes

Reaction equation

HRID 423008 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:13][C:14]([C:16]2([NH:34]C(=O)OC(C)(C)C)[CH2:21][CH2:20][N:19]([C:22]3[C:23]4[C:30]([CH:31]5[CH2:33][CH2:32]5)=[CH:29][NH:28][C:24]=4[N:25]=[CH:26][N:27]=3)[CH2:18][CH2:17]2)=[O:15])[CH2:10][CH2:11][OH:12])=[CH:5][CH:4]=1>O1CCOCC1.CO>[NH2:34][C:16]1([C:14]([NH:13][C@H:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][CH:5]=2)[CH2:10][CH2:11][OH:12])=[O:15])[CH2:17][CH2:18][N:19]([C:22]2[C:23]3[C:30]([CH:31]4[CH2:32][CH2:33]4)=[CH:29][NH:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:20][CH2:21]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57750284(S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2×

Product 1

HCID 42602348(S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideYield 7.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Hydrogen chloride 4M in dioxane (0.923 mL, 3.69 mmol) was added to (S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 65) (420 mg, 0.74 mmol) in dioxane (25 mL). The resulting solution was stirred at ambient temperature for 2 hours. The reaction mixture was dissolved in methanol and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 3.5N ammonia/MeOH and pure fractions were evaporated to dryness. The product was then purified by preparative LCMS (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (25.0 mg, 7.2%) as a white solid.

Workup

  1. custompurified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customwere evaporated to dryness
  4. customThe product was then purified by preparative LCMS (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

Sources & evidence

ORD record
ord-2397b54be09c4b2db9e56ac551c5b687
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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