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 423008

반응식

HRID 423008 반응식
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

참가 물질

5

반응물 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-ylcarbamate2회

생성물 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-carboxamide수율 7.2%

시약·촉매·용매 2

HCID 887Methanol용매HCID 312751,4-Dioxane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2397b54be09c4b2db9e56ac551c5b687
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101623B2

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