Sodium borohydride → tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423055노트

반응식

HRID 423055 반응식
[BH4-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1([C:26]([NH:28][CH:29]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[CH2:30][C:31](OC)=[O:32])=[O:27])[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[CH:25]=[CH:24][NH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CCO.O>[Cl:41][C:38]1[CH:37]=[CH:36][C:35]([CH:29]([NH:28][C:26]([C:11]2([NH:10][C:8](=[O:9])[O:7][C:3]([CH3:5])([CH3:4])[CH3:6])[CH2:12][CH2:13][N:14]([C:17]3[C:18]4[CH:25]=[CH:24][NH:23][C:19]=4[N:20]=[CH:21][N:22]=3)[CH2:15][CH2:16]2)=[O:27])[CH2:30][CH2:31][OH:32])=[CH:40][CH:39]=1

참가 물질

5

반응물 2

HCID 4311764Sodium borohydrideHCID 57750359methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate2회

생성물 1

HCID 57750387tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate수율 30.1%

시약·촉매·용매 2

HCID 962Water촉매HCID 702Ethanol용매

반응 조건

온도
20 °C

실험 절차

Sodium borohydride (1.019 g, 26.93 mmol) was added in one portion to a stirred suspension of methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate (Intermediate 35) (1.0 g, 1.80 mmol) dissolved in EtOH (400 mL) under argon. The resulting suspension was stirred at 20° C. for 70 hours. A few drops of water were added to quench the excess of hydride and the mixture stirred for 1 hour. The mixture was evaporated to dryness and the residue was partitioned between CH2Cl2 and water saturated with NaCl. The organic phase was dried and concentrated to provide crude product as white crystals. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane. The pure fractions were evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (286 mg, 30.1%) as a white solid.

후처리

  1. customto quench the excess of hydride
  2. stirringthe mixture stirred for 1 hour
  3. customThe mixture was evaporated to dryness
  4. customthe residue was partitioned between CH2Cl2 and water saturated with NaCl
  5. customThe organic phase was dried
  6. concentrationconcentrated
  7. customto provide crude product as white crystals
  8. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane
  9. customThe pure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-31176b2569084376963103a80d864f8d
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101623B2

반응 노트

불러오는 중…