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

HRID 2175660Notes

Reaction equation

HRID 2175660 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[C:9](Br)[N:8]([C@@H:25]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:37]([Cu])#[N:38].N#N>CN(C=O)C>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[C:9]([C:37]#[N:38])[N:8]([C@@H:25]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 947NitrogenHCID 86719380(R)-tert-butyl 3-(4-amino-6-bromo-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylateHCID 178418546HCID 178418546, compound

Product 1

HCID 86719398(R)-tert-butyl 3-(4-amino-6-cyano-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylateYield 65.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A solution of (R)-tert-butyl 3-(4-amino-6-bromo-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (9) (200 mg, 0.36 mmol) and CuCN (110 mg, 1.08 mmol) in DMF (10 mL) was purged with N2 for three times. The resulting mixture was stirred at 160° C. overnight. After cooling to r.t., the reaction mixture was concentrated to obtain the crude product which was purified by flash chromatography (silica gel, 0 to 100% ethyl acetate in petroleum ether) to afford (R)-tert-butyl 3-(4-amino-6-cyano-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (101) (117 mg, 65% yield) as a yellow solid. LC-MS (ESI): m/z (M+1) 497.1.

Workup

  1. temperatureAfter cooling to r.t.
  2. concentrationthe reaction mixture was concentrated
  3. customto obtain the crude product which
  4. customwas purified by flash chromatography (silica gel, 0 to 100% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-475af1fdf44446769513c4fb9c363aa1
Source dataset
uspto-grants-2015_06
Patent number
US09062058B2

Reaction notes

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