Cesium carbonate → 4-(4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

HRID 1676208Notes

Reaction equation

HRID 1676208 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22](OC(C)(C)C)=O)[CH2:18][CH2:17]3)=[CH:11][C:10]2=[O:29])=[C:5]([F:30])[CH:4]=1)#[N:2].O=C1C=C(OC2CCN(C(OC(C)(C)C)=O)CC2)C=CN1C1C=NC=CC=1.ClC1[N:64]=[CH:63][C:62]([CH2:65][CH2:66][CH3:67])=[CH:61][N:60]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH:65]1([C:62]2[CH:61]=[N:60][C:22]([N:19]3[CH2:18][CH2:17][CH:16]([O:15][C:12]4[CH:13]=[CH:14][N:9]([C:6]5[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=5[F:30])[C:10](=[O:29])[CH:11]=4)[CH2:21][CH2:20]3)=[N:64][CH:63]=2)[CH2:67][CH2:66]1

Participants

6

Reactant 5

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 27357842-Chloro-5-propylpyrimidineHCID 57468410Tert-butyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateHCID 67367446Tert-butyl 4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 574684234-(4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

Conditions

Temperature
100 °C

Procedure

Example 190 was prepared according to procedures described in Example 132 substituting tert-butyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (Example 176) for tert-butyl 4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate in Step C and substituting 2-chloro-5-cyclopropylpyrimidine (prepared according to the procedure described in Step A of Example 159) for 2-chloro-5-propylpyrimidine and substituting potassium carbonate for cesium carbonate in Step D except that reaction was stirred at 100° C. for 7 h. The crude solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2). 1H NMR (500 MHz, CDCl3) δ ppm 8.14 (s, 2H), 7.51-7.62 (m, 3H), 7.11 (d, J=7.70 Hz, 1H), 6.06 (dd, J=7.70, 2.75 Hz, 1H), 6.01 (d, J=2.75 Hz, 1 H), 4.52-4.62 (m, 1H), 4.15-4.26 (m, 2H), 3.58-3.68 (m, 2H), 1.96-2.14 (m, 2 H), 1.79-1.96 (m, 2H), 1.69-1.77 (m, 1H), 0.88-0.96 (m, 2H), 0.57-0.64 (m, 2 H). MS (ESI) 432 (M+H).

Workup

  1. customExample 190 was prepared
  2. customprepared
  3. customThe crude solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-1eaeeba0f0d143ad9729b981e8c8963a
Source dataset
uspto-grants-2011_08
Patent number
US08003796B2

Reaction notes

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