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

HRID 2175662Notes

Reaction equation

HRID 2175662 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.[CH3:37][C:38]1(C)[C:42](C)(C)OB(C(C)=C)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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:38]([CH3:42])=[CH2:37])[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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 86719380(R)-tert-butyl 3-(4-amino-6-bromo-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86719400(R)-tert-butyl 3-(4-amino-5-(4-phenoxyphenyl)-6-(prop-1-en-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylateYield 85.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (R)-tert-butyl 3-(4-amino-6-bromo-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (9) (150 mg, 0.27 mmol), 4,4,5,5-tetra methyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (136 mg, 0.81 mmol), tetrakis (31 mg, 0.027 mmol) and Na2CO3 (0.40 mL, 2M solution in water) in dioxane (3.0 mL) was purged with N2 before heated at 80° C. overnight. After cooled down to r. t., the reaction mixture was concentrated under reduced pressure to give the crude product which was purified by column chromatographic (silica gel, 0 to 70% ethyl acetate in petroleum ether) to afford (R)-tert-butyl 3-(4-amino-5-(4-phenoxyphenyl)-6-(prop-1-en-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (116) (118 mg, 85% yield) as a brown solid. LC-MS (ESI): m/z (M+1) 512.1.

Workup

  1. customwas purged with N2
  2. temperatureAfter cooled down to r
  3. concentration, the reaction mixture was concentrated under reduced pressure
  4. customto give the crude product which
  5. customwas purified by column chromatographic (silica gel, 0 to 70% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-1207fcd9f2f141efbf991f85a228de07
Source dataset
uspto-grants-2015_06
Patent number
US09062058B2

Reaction notes

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