Triethylamine → Ethyl (2S)-2-(tert-butoxy)-2-[4,23-dimethyl-16-(trifluoromethyl)-11,22-dioxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,13(18),14,16,19-octaen-3-yl]acetate

HRID 921108Notes

Reaction equation

HRID 921108 reaction equation
[CH2:1]([O:4][C:5]1([CH3:46])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][C:24]=4Br)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(#N)C>[C:42]([O:41][C@@H:35]([C:12]1[C:13]([CH3:34])=[N:14][C:15]2=[CH:19][C:18]3=[N:17][N:16]2[C:11]=1[N:8]1[CH2:7][CH2:6][C:5]([CH3:46])([O:4][CH2:1][CH:2]=[CH:3][C:24]2[CH:25]=[C:26]([C:29]([F:32])([F:31])[F:30])[CH:27]=[CH:28][C:23]=2[CH2:22][O:21][CH2:20]3)[CH2:10][CH2:9]1)[C:36]([O:38][CH2:39][CH3:40])=[O:37])([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 118321378(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-bromo-4-(trifluoromethyl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 131734904Ethyl (2S)-2-(tert-butoxy)-2-[4,23-dimethyl-16-(trifluoromethyl)-11,22-dioxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,13(18),14,16,19-octaen-3-yl]acetateYield 63%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a pressure tube flushed with N2 were added (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-bromo-4-(trifluoromethyl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.200 g, 0.281 mmol), acetonitrile (8 ml) and triethylamine (0.392 ml, 2.81 mmol). Added to this solution were triphenylphosphine (0.022 g, 0.084 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.026 g, 0.028 mmol). The tube was sealed and stirred at 120° C. for 23 h. The mixture was cooled, filtered and concentrated to give a yellow residue that was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV) to give the title compound (0.1115 g, 0.177 mmol, 62.9% yield) as a yellow foam. LCMS (M+H) calcd for C34H44F3N4O4: 631.31. found: 631.3.

Workup

  1. customTo a pressure tube flushed with N2
  2. additionAdded to this solution
  3. customThe tube was sealed
  4. temperatureThe mixture was cooled
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a yellow residue that
  8. customwas purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV)

Sources & evidence

ORD record
ord-8345eb48d8fd4177a6b9184c63289342
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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