Potassium Carbonate → [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-[6-(2,2,2-trifluoro-ethoxy)-pyridin-3-ylmethyl]-amine

HRID 1754772Notes

Reaction equation

HRID 1754772 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([NH2:27])=[N:25][CH:26]=3)=[CH:11]2)(=O)=O)C=CC=CC=1.[F:28][C:29]([F:41])([F:40])[CH2:30][O:31][C:32]1[N:37]=[CH:36][C:35]([CH:38]=O)=[CH:34][CH:33]=1.C([BH3-])#N.[OH-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(O)C.C(O)(=O)C>[Cl:19][C:17]1[CH:18]=[C:13]2[C:12]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([NH:27][CH2:38][C:35]4[CH:36]=[N:37][C:32]([O:31][CH2:30][C:29]([F:41])([F:28])[F:40])=[CH:33][CH:34]=4)=[N:25][CH:26]=3)=[CH:11][NH:10][C:14]2=[N:15][CH:16]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 498716Cyano-borohydrideHCID 216984996-(2,2,2-Trifluoroethoxy)nicotinaldehydeHCID 576192232-Pyridinamine, 5-[[5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methyl]-

Product 1

HCID 57619476[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-[6-(2,2,2-trifluoro-ethoxy)-pyridin-3-ylmethyl]-amineYield 7.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

To 5-(1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine (599, 124.1 mg, 0.31 mmol, prepared as described in Example 68, Scheme 185) in ethanol (3.00 mL) and acetic acid (0.2 mL) were added 6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbaldehyde (603, 164.0 mg, 0.80 mmol) and silica supported cyanoborohydride (1.21 mmol/g, 0.700 g). The reaction was irradiated with microwave on 300 watts, 100° C. for 150 minutes. To the reaction was added a solution of potassium hydroxide (9.0 M in water, 1.0 mL). The reaction was irradiated with microwave on 300 watts, 100° C. for 10 minutes. The reaction was poured into aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (P-0409, 10.6 mg, 7.6%). MS ESI) [M+H+]+=448.4.

Workup

  1. customThe reaction was irradiated with microwave on 300 watts, 100° C. for 150 minutes
  2. customThe reaction was irradiated with microwave on 300 watts, 100° C. for 10 minutes
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 20% to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e22e6e63bee7450780d2c9248d22714f
Source dataset
uspto-grants-2015_10
Patent number
US09169250B2

Reaction notes

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