Chlorosuccinimide → (R)-tert-butyl 3-(4-amino-6-chloro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

HRID 510333Notes

Reaction equation

HRID 510333 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH2:22])[C:16]=3[C:15]([C:23]3[CH:28]=[CH:27][C:26]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:25][CH:24]=3)=[CH:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Cl:43])C(=O)C1>C(Cl)Cl>[NH2:22][C:21]1[C:16]2[C:15]([C:23]3[CH:24]=[CH:25][C:26]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:27][CH:28]=3)=[C:14]([Cl:43])[N:13]([C@@H:10]3[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]3)[C:17]=2[N:18]=[CH:19][N:20]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 86719376(R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86719379(R)-tert-butyl 3-(4-amino-6-chloro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylateYield 40.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-tert-butyl 3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (2) (350 mg, 0.74 mmol) in DCM (10.0 mL) was added NCS (198 mg, 1.48 mmol). After the mixture was stirred at r.t. for 6 hr the reaction solution was partitioned between DCM (20.0 mL) and water (20.0 mL). The layers were separated and the organic phase was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatographic (silica gel, 0-50% ethyl acetate in a mixture of petroleum ether and DCM (1:1)) to afford (R)-tert-butyl 3-(4-amino-6-chloro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (6) (150 mg, 40% yield) as a yellow oil. LC-MS (ESI): m/z (M/M+2) 506.1/508.1.

Workup

  1. customwas partitioned between DCM (20.0 mL) and water (20.0 mL)
  2. customThe layers were separated
  3. washthe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude product which
  7. customwas purified by column chromatographic (silica gel, 0-50% ethyl acetate
  8. additionin a mixture of petroleum ether and DCM (1:1))

Sources & evidence

ORD record
ord-6c11f1868c4545049026151b2211499a
Source dataset
uspto-grants-2015_08
Patent number
US09096604B2

Reaction notes

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