Hydrogen Bromide → (1S,2S,4R)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentan-1-ol

HRID 1427336노트

반응식

HRID 1427336 반응식
Cl[C:2]1[C:7]([CH2:8][CH:9](OCC)OCC)=[C:6]([Cl:16])[N:5]=[CH:4][N:3]=1.[NH2:17][C@H:18]1[CH2:22][C@H:21]([OH:23])[C@H:20]([CH2:24][OH:25])[CH2:19]1.Br.C(O)(C)C.C(N(CC)CC)C.Cl.C(=O)(O)[O-].[Na+]>O>[Cl:16][C:6]1[C:7]2[CH:8]=[CH:9][N:17]([C@H:18]3[CH2:22][C@H:21]([OH:23])[C@H:20]([CH2:24][OH:25])[CH2:19]3)[C:2]=2[N:3]=[CH:4][N:5]=1

참가 물질

9

반응물 7

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 197943054,6-Dichloro-5-(2,2-diethoxyethyl)pyrimidineHCID 57572816(1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol

생성물 1

HCID 57336811(1S,2S,4R)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentan-1-ol

시약·촉매·용매 1

HCID 962Water용매2회

반응 조건

온도
85 °C

실험 절차

To a slurry of 4,6-dichloro-5-(2,2-diethoxyethyl)pyrimidine (10.0 g, 0.0377 mol) and (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol.HBr (800 g) in isopropyl alcohol (82 mL, 1.1 mol) and water (11 mL, 0.59 mol), triethylamine (13 mL, 0.094 mol) was added. This mixture was then heated to 85° C. for 23 hours. The mixture was cooled to 50° C., at which point 4M hydrochloric acid in water (20 mL) was added slowly. The resulting mixture was then stirred at 50° C. for 3 hours. HPLC indicated that the reaction was complete. The reaction mixture was cooled to ambient temperature and sodium bicarbonate (10 g, 0.1 mol) was added portionwise. Excess solids were filtered; the bed washed with isopropyl alcohol (20 mL) and the filtrate concentrated to ˜70 mL. Ethyl acetate (150 mL) was added followed by a mixture of saturated NaHCO3 aq (35 mL) and water (35 mL). The layers were separated and the aqueous phases extracted with ethyl acetate (2×50 mL) and filtered. The organic layers were combined and washed with saturated NaCl aq (50 mL) and then concentrated to afford the title compound (90.3 g) as a brown solid. 1H NMR (300 MHz, CD3OD, δ): 8.56 (s, 1H), 7.67 (d, 1H), 6.65 (d, 1H), 5.52 (m, 1H), 4.50 (m, 1H), 3.79 (m, 1H), 3.66 (m, 1H), 2.63 (m, 1H), 2.25 (m, 3H) and 2.02 (m, 1H).

후처리

  1. additionwas added slowly
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationExcess solids were filtered
  4. washthe bed washed with isopropyl alcohol (20 mL)
  5. concentrationthe filtrate concentrated to ˜70 mL
  6. additionEthyl acetate (150 mL) was added
  7. additionfollowed by a mixture of saturated NaHCO3 aq (35 mL) and water (35 mL)
  8. customThe layers were separated
  9. extractionthe aqueous phases extracted with ethyl acetate (2×50 mL)
  10. filtrationfiltered
  11. washwashed with saturated NaCl aq (50 mL)
  12. concentrationconcentrated

출처 및 근거

ORD 기록
ord-afd3eb4783c64c25a46c59677d93e850
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933225B2

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