Dimethylformamide → (S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4'-fluoro-2'-hydroxy-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400766Notes

Reaction equation

HRID 1400766 reaction equation
[CH2:1]([O:4][C:5]1([CH3:39])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[F:40][C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[C:43]([OH:50])[CH:42]=1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=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>[CH2:1]([O:4][C:5]1([CH3:39])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:44]5[CH:45]=[CH:46][C:41]([F:40])=[CH:42][C:43]=5[OH:50])[CH:23]=[CH:24][CH:25]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 3865312(4-Fluoro-2-hydroxy)phenylboronic acidHCID 86710813(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 86710819(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4'-fluoro-2'-hydroxy-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 68%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.38 g, 0.63 mmol, 1 equiv), (4-fluoro-2-hydroxyphenyl)boronic acid (148 mg, 0.95 mmol, 1.5 equiv), and Pd(PPh3)4 (73 mg, 0.063 mmol, 0.1 equiv) was added DMF (6.3 mL that had been degassed by sparging with nitrogen for 10 min) Na2CO3 (0.63 mL of a 2 M aqueous solution, 1.27 mmol, 2 equiv) was added and the reaction was heated to 90° C. for 18 h. Upon cooling to ambient temperature, the reaction was diluted with EtOAc and washed with water. The EtOAc layer was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc in hexane) to provide the product as a yellow glass (0.27 g, 68%). LCMS (M+1)=631.4.

Workup

  1. additionwas added
  2. temperatureUpon cooling to ambient temperature
  3. washwashed with water
  4. dry with materialThe EtOAc layer was dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (0-100% EtOAc in hexane)

Sources & evidence

ORD record
ord-e4edc0a318914a20a0029ecf815ff376
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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