Ammonium Chloride → Carbamic acid, N-[4-chloro-5-[[5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]hydroxymethyl]-2-thiazolyl]-, 1,1-dimethylethyl ester

HRID 509933Notes

Reaction equation

HRID 509933 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[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:26]([O:30][C:31](=[O:41])[NH:32][C:33]1[S:34][C:35]([CH:39]=[O:40])=[C:36]([Cl:38])[N:37]=1)([CH3:29])([CH3:28])[CH3:27].[Cl-].[NH4+]>O1CCCC1>[C:26]([O:30][C:31](=[O:41])[NH:32][C:33]1[S:34][C:35]([CH:39]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=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:40])=[C:36]([Cl:38])[N:37]=1)([CH3:29])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 242292391-Benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridineHCID 45117878Tert-butyl (4-chloro-5-formylthiazol-2-yl)carbamate2×HCID 178418918HCID 178418918, compound2×

Product 1

HCID 57619425Carbamic acid, N-[4-chloro-5-[[5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]hydroxymethyl]-2-thiazolyl]-, 1,1-dimethylethyl esterYield 60.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-25 °C

Procedure

To a solution of 1-benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine (12, 4.40 g, 10.5 mmol) in 30.0 mL of tetrahydrofuran at −45° C. under nitrogen, a solution of isopropylmagnesium chloride (5.4 mL, 2.0 M in tetrahydrofuran) was added slowly over 10 minutes. The reaction was allowed to warm to −25° C. over 30 minutes, then cooled to −65° C., followed by adding the cold deprotonated (4-chloro-5-formyl-thiazol-2-yl)-carbamic acid tert-butyl ester, which was prepared in situ by adding isopropylmagnesium chloride (5.0 mL, 2.0 M in tetrahydrofuran) to (4-chloro-5-formyl-thiazol-2-yl)-carbamic acid tert-butyl ester (26, 2.51 g, 9.55 mmol) in 23.0 mL of tetrahydrofuran at −78° C. under nitrogen. The reaction was allowed to warm to room temperature over 2 hours, then poured into aqueous ammonium chloride, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 25-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (27, 3.70 g, 60.3%). MS (ESI) [M+H+]+=554.2.

Workup

  1. temperaturecooled to −65° C.
  2. customwas prepared in situ
  3. temperatureto warm to room temperature over 2 hours
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with 25-100% ethyl acetate in hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-089815ed2f214dc18103f47882d48eab
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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