Hydrochloric Acid → 4-{1-[1-(ethylsulfonyl)-3-(fluoromethyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

HRID 1966197Notes

Reaction equation

HRID 1966197 reaction equation
[F:1][CH2:2][C:3]1([N:14]2[CH:18]=[C:17]([C:19]3[C:20]4[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:21]=4[N:22]=[CH:23][N:24]=3)[CH:16]=[N:15]2)[CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4]1.Cl.O1CCOCC1.C(#N)C.C(N(CC)CC)C.[CH2:53]([S:55](Cl)(=[O:57])=[O:56])[CH3:54]>>[CH2:53]([S:55]([N:5]1[CH2:6][C:3]([N:14]2[CH:18]=[C:17]([C:19]3[C:20]4[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:33])[CH3:35])[C:21]=4[N:22]=[CH:23][N:24]=3)[CH:16]=[N:15]2)([CH2:2][F:1])[CH2:4]1)(=[O:57])=[O:56])[CH3:54]

Participants

7

Reactant 6

HCID 313Hydrochloric Acid2×HCID 6342AcetonitrileHCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 312751,4-DioxaneHCID 66824231tert-butyl 3-(fluoromethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

Product 1

HCID 668242874-{1-[1-(ethylsulfonyl)-3-(fluoromethyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Procedure

tert-Butyl 3-(fluoromethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (0.120 g, 0.239 mmol) was treated with 4.00 M of hydrogen chloride in 1,4-dioxane (1.0 mL, 4.0 mmol) at rt for 1 h, then evaporated to dryness under reduced pressured. LCMS (M+H) 403.4. To the resultant crude HCl salt in acetonitrile (4 mL, 80 mmol) was added triethylamine (0.0998 mL, 0.716 mmol) followed by ethanesulfonyl chloride (0.0317 mL, 0.334 mmol). The mixture was stirred at rt for 30 min. After quenching with aq. sodium bicarbonate, the mixture was extracted with dichloromethane. The combined organic layers were washed with water, brine and dried over sodium sulfate, evaporated to dry. The residue was used directly in next step. LCMS calculated for C21H32FN6O3SSi(M+H)+: m/z=495.2. Found: 495.4.

Workup

  1. customevaporated to dryness under reduced pressured
  2. customAfter quenching with aq. sodium bicarbonate
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customto dry

Sources & evidence

ORD record
ord-218fd894ef8b47dba79e6b146f12b47c
Source dataset
uspto-grants-2013_04
Patent number
US08420629B2

Reaction notes

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