Cesium carbonate → (3R*,4R*)-N-(5-fluorothiazolo[5,4-b]pyridin-2-yl)-4'H-1-azaspiro[bicyclo[2.2.1]heptane-3,5'-oxazol]-2'-amine

HRID 2059816Notes

Reaction equation

HRID 2059816 reaction equation
[F:1][C:2]1[N:7]=[C:6]2[S:8][C:9]([N:11]=[C:12](SC)SC)=[N:10][C:5]2=[CH:4][CH:3]=1.Cl.Cl.[NH2:19][CH2:20][C@@:21]1([OH:28])[C@H:26]2[CH2:27][N:23]([CH2:24][CH2:25]2)[CH2:22]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.C(Cl)(Cl)Cl>[F:1][C:2]1[N:7]=[C:6]2[S:8][C:9]([NH:11][C:12]3[O:28][C@@:21]4([C@H:26]5[CH2:27][N:23]([CH2:24][CH2:25]5)[CH2:22]4)[CH2:20][N:19]=3)=[N:10][C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 57516879(3S*,4R*)-3-(aminomethyl)-1-azabicyclo[2.2.1]heptan-3-ol dihydrochlorideHCID 59286681Dimethyl (5-fluorothiazolo[5,4-b]pyridin-2-yl)carbonimidodithioate

Product 1

HCID 86658780(3R*,4R*)-N-(5-fluorothiazolo[5,4-b]pyridin-2-yl)-4'H-1-azaspiro[bicyclo[2.2.1]heptane-3,5'-oxazol]-2'-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of dimethyl 5-fluorothiazolo[5,4-b]pyridin-2-ylcarbonimidodithioate (95 mg, 0.349 mmol) in N,N-dimethylformamide (2 mL) was added (3S*,4R*)-3-(aminomethyl)-1-azabicyclo[2.2.1]heptan-3-ol dihydrochloride (75 mg, 0.349 mmol). The reaction was then treated with cesium carbonate (114 mg, 0.7 mmol). The reaction was heated to 100° C. for 1 hour and then cooled to room temperature. The reaction was diluted with water (20 mL) and chloroform (2×20 mL). The organic phases were combined and concentrated to residue in vacuo. The residue was then triturated in diethyl ether to give (3R*,4R*)—N-(5-fluorothiazolo[5,4-b]pyridin-2-yl)-4′H-1-azaspiro[bicyclo[2.2.1]heptane-3,5′-oxazol]-2′-amine as a precipitate (42 mg, 37%) that was collected via vacuum filtration. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.13 (br. s., 1H) 8.07 (dd, J=8.53, 7.28 Hz, 1H) 7.16 (dd, J=8.53, 1.51 Hz, 1H) 3.85 (d, J=10.29 Hz, 1H) 3.66 (d, J=10.29 Hz, 1H) 2.77-2.98 (m, 2H) 2.71 (td, J=6.65, 4.02 Hz, 2H) 2.58-2.67 (m, 2H) 2.40 (dd, J=10.16, 3.64 Hz, 1H) 1.87-2.00 (m, 1H) 1.53 (t, J=4.39 Hz, 1H). MS (LC/MS) R.T.=0.675 min; (M+H=320.1).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated to residue in vacuo
  3. customThe residue was then triturated in diethyl ether

Sources & evidence

ORD record
ord-3dbb31bd3cb14aeb9615ebd554795fb3
Source dataset
uspto-grants-2012_10
Patent number
US08278320B2

Reaction notes

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