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

HRID 510332Notes

Reaction equation

HRID 510332 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].[B-](F)(F)(F)[F:37].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>CC#N>[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]([F:37])[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 2724933SelectfluorHCID 86719376(R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86719378(R)-tert-butyl 3-(4-amino-6-fluoro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylateYield 17%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of (R)-tert-butyl 3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (2) (1.0 g, 2.1 mmol) in MeCN (30.0 mL) was cooled to 0° C. with ice bath. Selectfluor (1.5 g, 4.2 mmol) was added to the reaction mixture in one portion. After addition, the ice-water bath was removed, and the stifling was continued for 1 hr at r. t. The reaction mixture was susequently partitioned between water (30 mL) and DCM (50 mL). The layers were separated and the aqueous phase was extracted with DCM (10 mL×3). Combined organic phases were 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 to 50% ethyl acetate in DCM) to afford (R)-tert-butyl 3-(4-amino-6-fluoro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (3) (175 mg, 17% yield) as a yellow solid. LC-MS (ESI): (M+1) 490.1.

Workup

  1. additionAfter addition
  2. customthe ice-water bath was removed
  3. customThe reaction mixture was susequently partitioned between water (30 mL) and DCM (50 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with DCM (10 mL×3)
  6. washCombined organic phases were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto obtain the crude product which
  10. customwas purified by column chromatographic (silica gel, 0 to 50% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-37c53b26221e4eb9b604cf1f7b156ef2
Source dataset
uspto-grants-2015_08
Patent number
US09096604B2

Reaction notes

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