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

HRID 2175640Notes

Reaction equation

HRID 2175640 reaction equation
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[O:24]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C@@H:12]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([C:34]3[CH:35]=[CH:36][C:31]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:32][CH:33]=3)=[CH:9]2)[CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 67035017(R)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86719376(R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylateYield 60%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (1) (2.0 g, 4.66 mmol), 4-phenoxyphenylboronic acid (1.3 g, 6.06 mmol), Pd(dppf)Cl2 (190 mg, 0.23 mmol) and Na2CO3 (1.9 g, 14.0 mmol) in DME (35.0 mL) and H2O (15.0 mL) was heated at 90° C. under N2 atmosphere overnight. After cooled down to r. t., the reaction mixture was diluted with water (50.0 mL) and DCM (50.0 mL). The layers were separated and the aqueous phase was extracted with DCM (25 mL×1). 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, 0-80% ethyl acetate in petroleum ether (“PE”) with DCM (1:1)) to afford (R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (2) (1.3 g, 60% yield) as a yellow solid. LC-MS (ESI): (M+1) 472.1.

Workup

  1. temperatureAfter cooled down to r
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with DCM (25 mL×1)
  4. washCombined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude product which
  8. customwas purified by column chromatographic (silica gel, 0-80% ethyl acetate in petroleum ether (“PE”) with DCM (1:1))

Sources & evidence

ORD record
ord-74518ca87f89489b9a9603bec0305fcd
Source dataset
uspto-grants-2015_06
Patent number
US09062058B2

Reaction notes

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