Dimethylformamide → HCID 67437168, compound

HRID 335927Notes

Reaction equation

HRID 335927 reaction equation
[F:1][C:2]([F:33])([F:32])S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:26]4[CH2:27][CH2:28][O:29][CH2:30][CH:31]=4)=[CH:16][C:17]=3[C@@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[CH:9][CH:8]=1)(=O)=O.[F:34][C:35]1[C:40](B(O)O)=[CH:39][CH:38]=[CH:37][N:36]=1.CN(C=O)C.[C:49](=O)([O-:51])[O-:50].[Na+].[Na+]>O.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>[F:33][C:2]([F:1])([F:32])[C:49]([OH:51])=[O:50].[O:29]1[CH2:30][CH:31]=[C:26]([C:15]2[CH:14]=[CH:13][C:12]3[O:11][C:10]4[C:19](=[CH:20][C:7]([C:40]5[C:35]([F:34])=[N:36][CH:37]=[CH:38][CH:39]=5)=[CH:8][CH:9]=4)[C@@:18]4([CH2:24][O:23][C:22]([NH2:25])=[N:21]4)[C:17]=3[CH:16]=2)[CH2:27][CH2:28]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 86658491HCID 86658491, compound

Product 1

HCID 67437168HCID 67437168, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A resealable vial was charged with (R)-2-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (100 mg, 0.207 mmol; prepared by method AA1 as described in Example 2), tetrakis(triphenylphosphine)palladium (23.95 mg, 0.021 mmol) and 2-fluoropyridin-3-ylboronic acid (0.332 mmol). DMF (1036 μL) was added followed by 2 M aqueous sodium carbonate (311 μL, 0.622 mmol) and the vial was sealed and heated at 85° C. for 1 hr. The mixture was cooled to the RT, diluted with water (2 ml) and EtOAc (5 ml). The organic layer was loaded onto 2 g SCX-2 column and washed with ethyl acetate and MeOH. The material was released from the column using 2M ammonia in MeOH solution, concentrated and purified by reverse phase HPLC (Gilson, 15-90% MeCN in 0.1% aq. TFA) to afford (R)-2′-(3,6-dihydro-2H-pyran-4-yl)-7′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine 2,2,2-trifluoroacetate.

Workup

  1. customthe vial was sealed
  2. temperatureThe mixture was cooled to the RT
  3. washwashed with ethyl acetate and MeOH
  4. concentrationconcentrated
  5. custompurified by reverse phase HPLC (Gilson, 15-90% MeCN in 0.1% aq. TFA)

Sources & evidence

ORD record
ord-f48da6b4e0794641941a71deba57fa23
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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