Triethylamine → Ethyl (2S)-2-(tert-butoxy)-2-[4,23-dimethyl-22-oxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,10,13(18),14,16,19-nonaen-3-yl]acetate

HRID 921104Notes

Reaction equation

HRID 921104 reaction equation
[CH2:1]([O:4][C:5]1([CH3:42])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH:20]=[CH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4Br)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:30])[C:12]=2[C@H:31]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[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:38]([O:37][C@@H:31]([C:12]1[C:13]([CH3:30])=[N:14][C:15]2=[CH:19][C:18]3=[N:17][N:16]2[C:11]=1[N:8]1[CH2:9][CH2:10][C:5]([CH3:42])([O:4][CH2:1][CH:2]=[CH:3][C:28]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH:21]=[CH:20]3)[CH2:6][CH2:7]1)[C:32]([O:34][CH2:35][CH3:36])=[O:33])([CH3:40])([CH3:41])[CH3:39]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 123595847(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-(2-bromophenyl)prop-1-en-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 123747350Ethyl (2S)-2-(tert-butoxy)-2-[4,23-dimethyl-22-oxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.02,7.013,18]octacosa-2,4,6(28),8,10,13(18),14,16,19-nonaen-3-yl]acetateYield 51.8%

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-(3-(2-bromophenyl)prop-1-en-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.09 g, 0.141 mmol), acetonitrile (4 ml) and triethylamine (0.196 ml, 1.407 mmol). Added to this solution were triphenylphosphine (0.011 g, 0.042 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.013 g, 0.014 mmol). The tube was sealed and stirred at 120° C. After stirring for 20 h, the mixture was cooled, filtered and concentrated to give a yellow residue. The residue was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV) to give the title compound (0.0406 g, 0.073 mmol, 51.6% yield) as a sticky yellow oil. LCMS (M+H) calcd for C33H43N4O4: 559.32. found: 559.5.

Workup

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

Sources & evidence

ORD record
ord-eda557132f6640199dcc38ed95c73f14
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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