Sodium Carbonate → (2S)-Methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2'-(but-3-en-1-yl)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400722Notes

Reaction equation

HRID 1400722 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:31])[C:16]=3[C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35][CH3:36])=[O:34])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3].[CH2:42]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1B(O)O)[CH2:43][CH:44]=[CH2:45].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]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:25]=[C:26]([C:47]6[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=6[CH2:42][CH2:43][CH:44]=[CH2:45])[CH:27]=[CH:28][CH:29]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:31])[C:16]=3[C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35][CH3:36])=[O:34])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 86710751(2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateHCID 86710753(2-(But-3-en-1-yl)phenyl)boronic acid

Product 1

HCID 86710772(2S)-Methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2'-(but-3-en-1-yl)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 100%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.092 g, 0.143 mmol), (2-(but-3-en-1-yl)phenyl)boronic acid (0.050 g, 0.286 mmol) and 2.0 M aq. Na2CO3 (0.179 mL, 0.358 mmol) in DMF (4 mL) was sparged with nitrogen for 10 min, treated with Pd(Ph3P)4 (0.012 g, 10.01 μmol), sparged for 5 min, then heated (90° C.) for 5 h. The reaction was cooled, then diltued with EtOAc (20 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated and the residue was purified by biotage (Isco 4 g SiO2, 0% (5 CV), 0-60% (20 CV), 60% (5 CV), EtOAc in hexanes) to afford the desired product (0.099 g, 0.143 mmol, 100% yield). LCMS (M+H)=691.4.

Workup

  1. customsparged for 5 min
  2. temperatureThe reaction was cooled
  3. washwashed with water (10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by biotage (Isco 4 g SiO2, 0% (5 CV), 0-60% (20 CV), 60% (5 CV), EtOAc in hexanes)

Sources & evidence

ORD record
ord-9571a63fadee4fce9f2e057d552531f4
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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