Sodium Carbonate → HCID 66692989, compound

HRID 472877Notes

Reaction equation

HRID 472877 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:31])=[N:13][C:14]2[N:15]([N:18]=[C:19]([C:21]3[CH:30]=[CH:29][C:28]4[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=4[CH:22]=3)[CH:20]=2)[C:16]=1Cl)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:32][C:33]1[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[C:36]([CH3:43])=[C:37]2[C:42]=1[O:41][CH2:40][CH2:39][CH2:38]2.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:31])=[N:13][C:14]2[N:15]([N:18]=[C:19]([C:21]3[CH:30]=[CH:29][C:28]4[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=4[CH:22]=3)[CH:20]=2)[C:16]=1[C:35]1[C:36]([CH3:43])=[C:37]2[C:42](=[C:33]([F:32])[CH:34]=1)[O:41][CH2:40][CH2:39][CH2:38]2)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 596067662-(8-Fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86670289HCID 86670289, compound

Product 1

HCID 66692989HCID 66692989, compoundYield 41.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (50 mg, 0.113 mmol), 2-(8-fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (36.4 mg, 0.124 mmol) and 2M Na2CO3 (0.113 mL, 0.226 mmol) in DMF (1.5 mL) was added tetrakis(triphenylphosphine)pallafium(0) (13.07 mg, 0.011 mmol) and the mixture was subjected to microwave heating at 120° C. for 1 h. The mixture was then filtered and purified by prep HPLC to afford atrope isomer 1 (major, first eluting): (2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (27 mg, 0.047 mmol, 41.7% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ: 7.56 (d, J=7.9 Hz, 1H), 7.52 (s, 1H), 7.09 (d, J=7.9 Hz, 1H), 6.92 (d, J=10.7 Hz, 1H), 6.84 (s, 1H), 5.03 (s, 1H), 4.41-4.32 (m, 2H), 3.66 (s, 3H), 2.88-2.78 (m, 6H), 2.77 (s, 3H), 2.26-2.17 (m, 2H), 1.86 (s, 3H), 1.85-1.79 (m, 4H), 1.19 (s, 9H).

Workup

  1. filtrationThe mixture was then filtered
  2. custompurified by prep HPLC
  3. customto afford
  4. washatrope isomer 1 (major, first eluting)

Sources & evidence

ORD record
ord-05ebdaa18fb94f448c957d81d5ba89cc
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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