Cesium fluoride → 1-(4-{4-[7-amino-2-(thieno[3,2-d]pyrimidin-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone

HRID 389550Notes

Reaction equation

HRID 389550 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[C:10]2[N:11]=[CH:12][N:13]=[CH:14][C:9]=2[S:8][CH:7]=1)CCC.[NH2:23][C:24]1[N:25]=[CH:26][C:27]([C:34]2[CH:35]=[N:36][N:37]([CH:39]3[CH2:44][CH2:43][N:42]([C:45](=[O:47])[CH3:46])[CH2:41][CH2:40]3)[CH:38]=2)=[C:28]2[CH:32]=[C:31](Cl)[O:30][C:29]=12.[F-].[Cs+]>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>[NH2:23][C:24]1[N:25]=[CH:26][C:27]([C:34]2[CH:35]=[N:36][N:37]([CH:39]3[CH2:40][CH2:41][N:42]([C:45](=[O:47])[CH3:46])[CH2:43][CH2:44]3)[CH:38]=2)=[C:28]2[CH:32]=[C:31]([C:6]3[C:10]4[N:11]=[CH:12][N:13]=[CH:14][C:9]=4[S:8][CH:7]=3)[O:30][C:29]=12

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 66759397HCID 66759397, compoundHCID 667606477-(Tributylstannanyl)thieno[3,2-d]pyrimidine

Product 1

HCID 667600151-(4-{4-[7-amino-2-(thieno[3,2-d]pyrimidin-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanoneYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A portion of 7-(tributylstannanyl)thieno[3,2-d]pyrimidine (0.030 g, 0.071 mmol) was dissolved in DMF (0.8 mL), and the solution was degassed with nitrogen for 10 min. To this mixture was added 1-{4-[4-(7-amino-2-chlorofuro[2,3-c]pyridin-4-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (0.017 g, 0.047 mmol), Pd(PPh3)4 (0.0066 g, 0.0057 mmol) and cesium fluoride (0.0241 g, 0.159 mmol). The mixture was heated in a microwave reactor for 30 min at 130° C. Purification by MDP and then ISCO chromatography (0 to 20% methanol:DCM) afforded 0.006 g (30%) of the title compound an off-white solid. 1H NMR (400 MHz, CD3OD): δ 9.53 (s, 1 H), 9.36 (s, 1 H), 8.94 (s, 1 H), 8.15 (s, 1 H), 8.03 (s, 1 H), 7.93 (s, 1 H), 7.91 (br. s., 1 H), 4.72 (d, J=13.1 Hz, 1 H), 4.65-4.54 (m, 2 H), 4.14 (d, J=9.6 Hz, 1 H), 2.90 (dt, J=2.8, 13.0 Hz, 1 H), 2.33-2.22 (m, 2 H), 2.20 (s, 3 H), 2.19-2.11 (m, 1 H), 2.10-1.97 (m, 1 H); MS (ESI): 460.36 [M+H]+.

Workup

  1. customthe solution was degassed with nitrogen for 10 min
  2. customPurification by MDP

Sources & evidence

ORD record
ord-75f1d30cc088431cb623be912fd943d7
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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