Oxazole → HCID 86719404, compound

HRID 2175665Notes

Reaction equation

HRID 2175665 reaction equation
Br[C:2]1[N:18]([C@@H:19]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]2)[C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10]C(OC(C)(C)C)=O)[C:4]=2[C:3]=1[C:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:33][CH:32]=1.[O:44]1[CH:48]=[CH:47][N:46]=[CH:45]1.CC([O-])(C)C.[K+]>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>[NH2:10][C:9]1[C:4]2[C:3]([C:31]3[CH:36]=[CH:35][C:34]([O:37][C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)=[CH:33][CH:32]=3)=[C:2]([C:45]3[O:44][CH:48]=[CH:47][N:46]=3)[N:18]([C@@H:19]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]3)[C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 9255OxazoleHCID 23665647Potassium tert-butoxideHCID 86719403HCID 86719403, compound

Product 1

HCID 86719404HCID 86719404, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of (R)-tert-butyl 3-(6-bromo-4-(tert-butoxycarbonylamino)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (119) (100 mg, 0.15 mmol), oxazole (52 mg, 0.75 mmol), t-BuOK (35 mg, 0.3 mmol) in dioxane (4 mL) was added tetrakis (36 mg, 0.03 mmol). The resulting mixture was purged with N2 (2×) before heated to 100° C. under N2 atmosphere for 30 hrs. The mixture was cooled down to r.t and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 0 to 50% EA in PE) to afford (R)-tert-butyl 3-(4-amino-6-(oxazol-2-yl)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (123) (30 mg, 42% yield) as a white solid. LC-MS (ESI): m/z (M+1) 539.1.

Workup

  1. customThe resulting mixture was purged with N2 (2×)
  2. temperatureThe mixture was cooled down
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (silica gel, 0 to 50% EA in PE)

Sources & evidence

ORD record
ord-d0916a31ddbd499788e906f5eca09308
Source dataset
uspto-grants-2015_06
Patent number
US09062058B2

Reaction notes

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