Sodium Bicarbonate → HCID 178508608, 화합물

HRID 51608

반응식

HRID 51608 반응식
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:24]3[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH:31]1[CH2:35][CH2:34][C@@H:33]([OH:36])[CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.C(Cl)Cl.CO.O>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:15][CH:16]=3)=[CH:9][N:8]([C@@H:24]3[CH2:29][CH2:28][C@H:27]([N:31]4[CH2:35][CH2:34][C@@H:33]([OH:36])[CH2:32]4)[CH2:26][CH2:25]3)[C:4]=2[N:5]=[CH:6][N:7]=1

참가 물질

9

반응물 4

HCID 516892Sodium BicarbonateHCID 2759337(R)-3-PyrrolidinolHCID 5049666Sodium triacetoxyborohydrideHCID 22736171Protein kinase inhibitor 9

생성물 1

HCID 178508608HCID 178508608, 화합물수율 44.6%

시약·촉매·용매 4

HCID 111,2-Dichloroethane용매HCID 887Methanol용매3회HCID 962Water용매HCID 6344Dichloromethane용매3회

실험 절차

A mixture of 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexanone (1.00 g, 2.51 mmol) and (R)-(+)-3-pyrrolidinol (0.62 mL, 7.5 mmol) in 1,2-dichloroethane (50 mL) was stirred at ambient temperature under an atmosphere of nitrogen for 1.5 hours. Sodium triacetoxyborohydride (0.691 g, 3.26 mmol) was added and the mixture stirred at ambient temperature for 22 hours. Water (50 mL) and sodium bicarbonate (1.34 g, 16.1 mmol) were added and the mixture was stirred for 2 hours. The reaction mixture was transferred to a separatory funnel and the organic layer was separated, dried over magnesium sulfate, filtered, and the solvent removed under reduced pressure to yield a yellow-brown solid. The cis isomer was purified by flash chromatography on silica gel (1 L 5% MeOH in CH2Cl2, then 2 L 10% MeOH in CH2Cl2, 1 L 20% MeOH in CH2Cl2, and 1 L 40% MeOH in CH2Cl2) to yield cis-(3R)-1-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}tetrahydro-1H-3-pyrrolol as a pale yellow oil (0.529 g, 1.12 mmol). The cis-(3R)-1-{4-[4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}tetrahydro-1H-3-pyrrolol (0.464 g, 0.988 mmol) was dissolved in warm ethanol (5 mL) and added to a solution of maleic acid (0.344 g, 2.96 mmol) in ethanol (5 mL). The mixture was cooled to ambient temperature then the solid was collected by filtration and dried to give cis-(3R)-1-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}tetrahydro-1H-3-pyrrolol dimaleate salt (0.549 g) as a pale yellow solid: 1H NMR (d6 DMSO, 400 MHz): δ H 8.22(1H, s), 7.41-7.50 (5H, m), 7.08-7.19(5H, m), 6.49(2H, bs), 6.13(4H, s), 4.85(1H, bs), 4.49(1H, bs), 3.37-3.68(5H, m), 1.92-2.18(11H, m); HPLC: (Hypersil HS C18, 5 μm, 254 nm, 250×4.6 mm; 25-100% acetonitrile-0.1N ammonium acetate over 10 min, 1 ml/min) tr=7.167 min.

후처리

  1. stirringthe mixture stirred at ambient temperature for 22 hours
  2. stirringthe mixture was stirred for 2 hours
  3. customThe reaction mixture was transferred to a separatory funnel
  4. customthe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customto yield a yellow-brown solid
  9. customThe cis isomer was purified by flash chromatography on silica gel (1 L 5% MeOH in CH2Cl2

출처 및 근거

ORD 기록
ord-dfbe8688b41a49a8931c396ca9bf3e6f
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06713474B2

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