Allyl bromide → HCID 86710787, compound

HRID 1400734Notes

Reaction equation

HRID 1400734 reaction equation
[CH:1](/[C:5]1([CH3:45])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=5[OH:33])[CH:23]=[CH:24][CH:25]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:36]([O:38][CH3:39])=[O:37])[CH2:7][CH2:6]1)=[CH:2]\[CH:3]=[CH2:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:53][CH:54]=[CH2:55]>CN(C=O)C>[CH2:55]([O:33][C:27]1[CH:28]=[CH:29][C:30]([Cl:32])=[CH:31][C:26]=1[C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:18]2[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]([C@H:35]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:36]([O:38][CH3:39])=[O:37])=[C:11]([N:8]4[CH2:7][CH2:6][C:5](/[CH:1]=[CH:2]/[CH:3]=[CH2:4])([CH3:45])[CH2:10][CH2:9]4)[N:16]3[N:17]=2)[CH:21]=1)[CH:54]=[CH2:53]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 86710785HCID 86710785, compound

Product 1

HCID 86710787HCID 86710787, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

.(S,E)-Methyl 2-(7-(4-(buta-1,3-dien-1-yl)-4-methylpiperidin-1-yl)-2-(5′-chloro-2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (90 mg, 0.143 mmol) was dissolved in DMF (3 mL). Solid K2CO3 (39.5 mg, 0.286 mmol) was added and the mixture was heated to 90° C. for 1 h. The reaction was then cooled to rt and treated with 3-bromoprop-1-ene (0.024 mL, 0.286 mmol) and allowed to stir at rt for 18 h. The reaction was partitioned between EtOAc and water. The organic phase was washed with water, dried (Na2SO4), filtered, and concentrated in vacuo to yield (S,E)-methyl 2-(2-(2′-(allyloxy)-5′-chloro-[1,1′-biphenyl]-3-yl)-7-(4-(buta-1,3-dien-1-yl)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (90 mg, 0.134 mmol, 94% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.18 (br. s., 1H), 8.07-8.00 (m, 1H), 7.60-7.48 (m, 2H), 7.42 (d, J=2.7 Hz, 1H), 7.31 (d, J=2.7 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 6.85 (s, 1H), 6.39 (dt, J=17.0, 10.1 Hz, 1H), 6.16 (dd, J=15.5, 10.1 Hz, 1H), 6.08 (s, 1H), 5.98 (ddt, J=17.3, 10.6, 4.8 Hz, 1H), 5.88 (d, J=15.7 Hz, 1H), 5.40-5.33 (m, 1H), 5.25-5.15 (m, 2H), 5.03 (d, J=10.0 Hz, 1H), 5.00-2.50 (m, 4 H), 4.56 (dt, J=4.8, 1.6 Hz, 2H), 3.74 (s, 3H), 2.64 (s, 3H), 1.97-1.63 (m, 4H), 1.32-1.23 (m, 12H). LCMS (M+1)=669.3.

Workup

  1. temperatureThe reaction was then cooled to rt
  2. customThe reaction was partitioned between EtOAc and water
  3. washThe organic phase was washed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-773826b5b0c148ee8142c8e440c16804
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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