Sodium Carbonate → (R)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxamide

HRID 2279599Notes

Reaction equation

HRID 2279599 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[N:9]=[CH:10][C:11]3[CH2:17][CH2:16][C@H:15]([C:18]([OH:20])=O)[O:14][C:12]=3[N:13]=2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Si:45]([O:52][CH2:53][C@H:54]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([F:63])[CH:57]=1)[NH2:55])([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46].CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(Cl)Cl>[Si:45]([O:52][CH2:53][C@@H:54]([NH:55][C:18]([C@@H:15]1[O:14][C:12]2[N:13]=[C:8]([NH:7][CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[N:9]=[CH:10][C:11]=2[CH2:17][CH2:16]1)=[O:20])[C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([F:63])[CH:57]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86705474(S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanamineHCID 86705581(R)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylic acid

Product 1

HCID 86705582(R)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxamideYield 48.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A vial was charged 408 (0.050 g, 0.15 mmol), HATU (0.069 g, 0.18 mmol), 68 (0.055 g, 0.18 mmol), DIPEA (1 mL), DCM (2 mL) and DMF (1 mL) and stirred for 18 h. To the solution was added satd. aq. Na2CO3 (5 mL), and the mixture stirred for 5 min. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography (SNAP 25) eluting with DCM/MeOH (95:5) to afford 0.041 g (43%) of (R)—N—((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxamide (410): MS m/z (APCI-pos) M+1=565.0.

Workup

  1. additionTo the solution was added satd
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by SiO2 chromatography (SNAP 25)
  7. washeluting with DCM/MeOH (95:5)

Sources & evidence

ORD record
ord-c20cbbe63f2f4323aa8443875fdad38f
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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