Sodium Carbonate → HCID 86710768, compound

HRID 1400715Notes

Reaction equation

HRID 1400715 reaction equation
[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[C:25](Br)[CH:24]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:30])[C:15]=3[C@H:31]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:32]([O:34][CH3:35])=[O:33])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3].[OH:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:43]6[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=6[OH:41])[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:30])[C:15]=3[C@H:31]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:32]([O:34][CH3:35])=[O:33])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2773454(2-Hydroxyphenyl)boronic acidHCID 86710765(2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 86710768HCID 86710768, compoundYield 80.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of ((2S)-methyl 2-(7-(4-allylchroman-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.430 g, 0.711 mmol), (2-hydroxyphenyl)boronic acid (0.196 g, 1.423 mmol) and 2.0 M aq. Na2CO3 (1.1 ml, 2.1 mmol) in DMF (7 ml) was sparged with nitrogen for 10 min, treated with Pd(Ph3P)4 (0.058 g, 0.050 mmol), then sparged for 5 min. The reaction was stirred for 90 min, then cooled, diluted with water (20 mL) and extracted into Et2O (2×50 mL). The combined extracts were dried (MgSO4), filtered, and concentrated and the residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes) to afford the desired product (0.360 g, 0.572 mmol, 80% yield) as a pale yellow glassy solid. 1H NMR (500 MHz, CDCl3) δ: 8.07-7.89 (m, 2H), 7.70 (s, 1H), 7.60-7.49 (m, 2H), 7.49-7.36 (m, 2H), 7.34-7.29 (m, 2H), 7.07-6.97 (m, 3H), 6.95-6.90 (m, 1H), 5.96-5.71 (m, 1H), 5.37-5.19 (m, 2H), 5.16-4.97 (m, 2H), 4.39-4.25 (m, 2H), 3.88-3.79 (m, 3H), 3.12-2.88 (m, 1H), 2.72-2.63 (m, 3H), 2.61-2.32 (m, 1H), 2.22-2.08 (m, 1H), 2.02-1.88 (m, 1H), 1.06-0.92 (m, 9H). LCMS (M+H)=618.5.

Workup

  1. customsparged for 5 min
  2. temperaturecooled
  3. additiondiluted with water (20 mL)
  4. extractionextracted into Et2O (2×50 mL)
  5. dry with materialThe combined extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes)

Sources & evidence

ORD record
ord-b5a4adc037194d1aab388e68d7a81075
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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