Cesium carbonate → HCID 50939922, compound

HRID 1039083Notes

Reaction equation

HRID 1039083 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[N:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)[CH2:19][CH2:18]2)(=O)=O)=CC=1.COC1C=CC(C[N:37]2[C:45]3[C:40](=[CH:41][C:42]([NH:46]C(=O)OC(C)(C)C)=[CH:43][CH:44]=3)[CH:39]=[N:38]2)=CC=1.COC1C=CC(CN2C3C(=CC(NC(=O)OC(C)(C)C)=CC=3)CN2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.O>[Cl:29][C:26]1[CH:27]=[N:28][C:23]([N:20]2[CH2:19][CH2:18][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][NH:46][C:42]3[CH:41]=[C:40]4[C:45](=[CH:44][CH:43]=3)[NH:37][N:38]=[CH:39]4)[CH2:22][CH2:21]2)=[N:24][CH:25]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 67962332HCID 67962332, compoundHCID 866661412-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonateHCID 86666145HCID 86666145, compound

Product 1

HCID 50939922HCID 50939922, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate from step 1 of Example 5 (100 mg, 0.23 mmol) was dissolved in NMP (1.1 ml). The mixture of tert-butyl [1-(4-methoxybenzyl)-1H-indazol-5-yl]carbamate and tert-butyl [1-(4-methoxybenzyl)-2H-indazol-5-yl]carbamate (81 mg, 0.23 mmol) from step 2 of this example and cesium carbonate (0.224 mg, 0.69 mmol) were added and the slurry stirred at 70° C. for 24 h. The mixture was diluted with 4:1 water:saturated sodium bicarbonate (30 ml), extracted with EtOAc (3×30 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered, and the volatiles removed in vacuum. The material was dissolved in TPA at RT and the solution stirred for 5 minutes. The solution was heated to 70° C. for 2 hours. The volatiles were removed in vacuum. The residue was dissolved in DCM (30 ml), shaken with a solution of saturated bicarbonate (30 ml), the layers separated, and the aqueous phase extracted with DCM (2×30 ml). The organic fractions were combined, washed with brine, dried over Na2SO4, filtered, and the volatiles removed in vacuum. The product was purified by chromatography on SiO2 eluting with 20% acetone:DCM to give the titled compound. LRMS calc: 396.18; obs: 397.27 (M+1). Compounds reported in Table 6 are prepared by a general procedure analogous to that described in Example 42 above.

Workup

  1. additionwere added
  2. extractionsaturated sodium bicarbonate (30 ml), extracted with EtOAc (3×30 ml)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe volatiles removed in vacuum
  7. dissolutionThe material was dissolved in TPA at RT
  8. stirringthe solution stirred for 5 minutes
  9. temperatureThe solution was heated to 70° C. for 2 hours
  10. customThe volatiles were removed in vacuum
  11. dissolutionThe residue was dissolved in DCM (30 ml)
  12. stirringshaken with a solution of saturated bicarbonate (30 ml)
  13. customthe layers separated
  14. extractionthe aqueous phase extracted with DCM (2×30 ml)
  15. washwashed with brine
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. customthe volatiles removed in vacuum
  19. customThe product was purified by chromatography on SiO2 eluting with 20% acetone

Sources & evidence

ORD record
ord-7ecb39db6d9147558028a0fae7442888
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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