Hydrochloric Acid → {5-[(7-benzenesulfonyl-4-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-hydroxy-methyl]-pyridin-2-yl}-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

HRID 1403268Notes

Reaction equation

HRID 1403268 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([CH:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)[C:13]=3[C:12](I)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[C:30]([O:34][C:35](=[O:56])[N:36]([C:48]1[CH:53]=[CH:52][C:51]([CH:54]=[O:55])=[CH:50][N:49]=1)[CH2:37][C:38]1[CH:39]=[N:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=1)([CH3:33])([CH3:32])[CH3:31].Cl>O1CCCC1>[C:30]([O:34][C:35](=[O:56])[N:36]([C:48]1[CH:53]=[CH:52][C:51]([CH:54]([C:12]2[C:13]3[C:18]([CH:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[N:17][CH:16]=[N:15][C:14]=3[N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH:11]=2)[OH:55])=[CH:50][N:49]=1)[CH2:37][C:38]1[CH:39]=[N:40][C:41]([C:44]([F:47])([F:45])[F:46])=[CH:42][CH:43]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 57963052(5-Formyl-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid tert-butyl esterHCID 579632347-benzenesulfonyl-4-cyclopentyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidineHCID 178418918HCID 178418918, compound

Product 1

HCID 57963233{5-[(7-benzenesulfonyl-4-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-hydroxy-methyl]-pyridin-2-yl}-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid tert-butyl esterYield 7.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To 7-benzenesulfonyl-4-cyclopentyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (50, 0.119 g, 0.262 mmol) in 1.8 mL of tetrahydrofuran at −20° C. under nitrogen, isopropylmagnesium chloride (0.144 mL, 2.0 M in tetrahydrofuran, 0.289 mmol) was added and the reaction stirred and allowed to warm to 0° C. over 1 hour. The reaction was cooled to −15° C. and (5-formyl-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (51, 0.120 g, 0.315 mmol) in 0.53 mL of tetrahydrofuran was added. The reaction was poured into 0.1 N aqueous hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with ethyl acetate and hexane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (52, 0.014 g). MS (ESI) [M+H+]+=709.6.

Workup

  1. temperatureThe reaction was cooled to −15° C.
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material was purified by silica gel column chromatography
  8. washeluting with ethyl acetate and hexane
  9. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-bef618b72c7d4d1ea393a6b53758709c
Source dataset
uspto-grants-2014_12
Patent number
US08912204B2

Reaction notes

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