Potassium Carbonate → HCID 86710785, compound

HRID 1400733Notes

Reaction equation

HRID 1400733 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:38]=[C:11]3[N:12]=[C:13]([CH3:37])[C:14]([C@H:27]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[C:28]([O:30][CH3:31])=[O:29])=[C:15]([N:16]4[CH2:21][CH2:20][C:19](/[CH:23]=[CH:24]/[CH:25]=[CH2:26])([CH3:22])[CH2:18][CH2:17]4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([OH:49])=[C:44](B(O)O)[CH:45]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[CH:23](/[C:19]1([CH3:22])[CH2:18][CH2:17][N:16]([C:15]2[N:10]3[N:9]=[C:8]([C:4]4[CH:3]=[C:2]([C:42]5[CH:41]=[C:40]([Cl:39])[CH:45]=[CH:44][C:43]=5[OH:49])[CH:7]=[CH:6][CH:5]=4)[CH:38]=[C:11]3[N:12]=[C:13]([CH3:37])[C:14]=2[C@H:27]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[C:28]([O:30][CH3:31])=[O:29])[CH2:21][CH2:20]1)=[CH:24]\[CH:25]=[CH2:26]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 23005362(5-Chloro-2-hydroxyphenyl)boronic Acid (contains varying amounts of Anhydride)HCID 86710786HCID 86710786, compound

Product 1

HCID 86710785HCID 86710785, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a microwave tube was added (S,E)-methyl 2-(2-(3-bromophenyl)-7-(4-(buta-1,3-dien-1-yl)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (100 mg, 0.172 mmol), (5-chloro-2-hydroxyphenyl)boronic acid (44.5 mg, 0.258 mmol), and 2.0 M aqueous K2CO3 (0.086 mL, 0.172 mmol) in dioxane (2 mL) and water (0.5 mL). The reaction was sparged with nitrogen for 1 minutes, treated Pd(PPh3)4 (19.87 mg, 0.017 mmol) then sparged for 1 min. The reaction tube was sealed and then heated at 90° C. in a microwave tube for 1 h. LCMS analysis showed 40% completion. Additional 10 mg of Pd(PPh3)4 added and heated at 90° C. for another 2 h. The reaction was concentrated, diluted with water (15 mL) and extracted wtih EtOAc. The EtOAc layer was washed with brine, then dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by biotage (0%-40% EtOAc in hexanes) to isolate 80 mg (74%) of the product as off-white foam. 1H NMR (500 MHz, CDCl3) δ 8.09 (br. s., 1H), 8.06 (d, J=7.9 Hz, 1H), 7.60 (t, J=7.5 Hz, 1H), 7.50-7.45 (m, 1H), 7.34 (d, J=2.5 Hz, 1H), 6.99 (d, J=8.7 Hz, 1H), 6.85 (s, 1H), 6.39 (dt, J=16.9, 10.2 Hz, 1H), 6.17 (dd, J=15.4, 10.4 Hz, 1H), 6.07 (s, 1H), 5.88 (d, J=15.3 Hz, 1H), 5.33 (br. s., 1H), 5.19 (d, J=17.2 Hz, 1H), 5.04 (d, J=9.6 Hz, 1H), 4.50-2.50 (m, 4 H), 3.75 (s, 3H), 2.64 (s, 3H), 1.93 (d, J=12.9 Hz, 1H), 1.87-1.73 (m, 2H), 1.67 (br. s., 1H), 1.29-1.24 (m, 12H). LCMS (M+1)=629.08.

Workup

  1. customThe reaction was sparged with nitrogen for 1 minutes
  2. customthen sparged for 1 min
  3. customThe reaction tube was sealed
  4. additionAdditional 10 mg of Pd(PPh3)4 added
  5. temperatureheated at 90° C. for another 2 h
  6. concentrationThe reaction was concentrated
  7. additiondiluted with water (15 mL)
  8. extractionextracted wtih EtOAc
  9. washThe EtOAc layer was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by biotage (0%-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b4a843656beb4a00b4d03db013a9337b
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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