Ammonium Chloride → Benzyl 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-4-carbonyl)piperidine-1-carboxylate

HRID 1506122Notes

Reaction equation

HRID 1506122 reaction equation
C([Mg]Cl)(C)C.I[C:7]1[C:8]2[CH:15]=[CH:14][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:9]=2[N:10]=[CH:11][N:12]=1.CC1C=CC=C(C)C=1[Mg]Br.CON(C)[C:37]([CH:39]1[CH2:44][CH2:43][CH2:42][N:41]([C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:46])[CH2:40]1)=[O:38].[Cl-].[NH4+]>O1CCCC1>[CH3:21][Si:20]([CH3:23])([CH3:22])[CH2:19][CH2:18][O:17][CH2:16][N:13]1[C:9]2[N:10]=[CH:11][N:12]=[C:7]([C:37]([CH:39]3[CH2:44][CH2:43][CH2:42][N:41]([C:45]([O:47][CH2:48][C:49]4[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=4)=[O:46])[CH2:40]3)=[O:38])[C:8]=2[CH:15]=[CH:14]1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 22258974Benzyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylateHCID 578708034-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidineHCID 178418918HCID 178418918, compoundHCID 178424791HCID 178424791, compound

Product 1

HCID 71137989Benzyl 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-4-carbonyl)piperidine-1-carboxylateYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Isopropylmagnesium chloride (2.0 M solution in tetrahydrofuran, 0.4 mL, 0.80 mmol) was gradually added dropwise to 4-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (200 mg, 0.530 mmol) obtained in Reference Synthetic Examplea 15 in tetrahydrofuran (3 mL) cooled to −78° C., and the resulting reaction mixture was stirred at −78° C. for 15 minutes. The reaction mixture was warmed to room temperature and stirred with (2,6-dimethylphenyl)magnesium bromide (1.0 M solution in tetrahydrofuran, 0.8 mL, 0.80 mmol) and benzyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate (245 mg, 0.800 mmol) in tetrahydrofuran (3.0 mL) at room temperature for 2.5 hours. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1→2/1→1/1 (v/v)) to give the title compound as a yellow oil (107 mg, yield 41%).

Workup

  1. customthe resulting reaction mixture
  2. temperatureThe reaction mixture was warmed to room temperature
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1→2/1→1/1 (v/v))

Sources & evidence

ORD record
ord-7cef0f8740bc4fdd81ffb1b747e4a3f1
Source dataset
uspto-grants-2015_12
Patent number
US09216999B2

Reaction notes

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