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

HRID 423022
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HRID 423022 반응식
Cl.O1CCOCC1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:23][C:24]([C:26]2([NH:41]C(=O)OC(C)(C)C)[CH2:31][CH2:30][N:29]([C:32]3[C:33]4[CH:40]=[CH:39][NH:38][C:34]=4[N:35]=[CH:36][N:37]=3)[CH2:28][CH2:27]2)=[O:25])[CH2:16][CH2:17][NH:18][S:19]([CH3:22])(=[O:21])=[O:20])=[CH:11][CH:10]=1.C(O)(C(F)(F)F)=O>>[NH2:41][C:26]1([C:24]([NH:23][CH:15]([C:12]2[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=2)[CH2:16][CH2:17][NH:18][S:19]([CH3:22])(=[O:20])=[O:21])=[O:25])[CH2:27][CH2:28][N:29]([C:32]2[C:33]3[CH:40]=[CH:39][NH:38][C:34]=3[N:35]=[CH:36][N:37]=2)[CH2:30][CH2:31]1
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참가 물질

5

반응물 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 312751,4-DioxaneHCID 57750389tert-butyl 4-(1-(4-chlorophenyl)-3-(methylsulfonamido)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2회

생성물 1

HCID 577503124-amino-N-(1-(4-chlorophenyl)-3-(methylsulfonamido)propyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
수율 65.3%

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온도
20 °C

실험 절차

HCl (4M) in 1,4-Dioxane (1.615 mL, 6.46 mmol) was added to tert-butyl 4-(1-(4-chlorophenyl)-3-(methylsulfonamido)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 117) (261 mg, 0.43 mmol), The resulting suspension was stirred at 20° C. for 1 hour. No reaction. TFA (1 mL) was then added to the reaction and stirred for 16 hours. The reaction was vacuumed to dryness and 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 [AP-HPLC Buffer]) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 4-amino-N-(1-(4-chlorophenyl)-3-(methylsulfonamido)propyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (142 mg, 65.2%) as a white solid.

후처리

  1. customNo reaction
  2. stirringstirred for 16 hours
  3. customwas purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. customwere evaporated to dryness
  6. customto afford crude material
  7. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-cb9d8d6930e9490483aa676daf590cc6
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08101623B2

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