Triethylamine → HCID 178455006, compound

HRID 931233Notes

Reaction equation

HRID 931233 reaction equation
[Si:1]([O:8][C:9]1([C:12]2[N:17]=[C:16]([C:18]#[N:19])[CH:15]=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[O-]CC.[Na+].Cl.Cl.N[C:27]1[CH:28]=[CH:29][C:30]([N:34]2[CH2:39][CH2:38][CH2:37][C@@H:36]([C:40]([N:42]3[CH2:46][CH2:45][CH2:44][CH2:43]3)=[O:41])[CH2:35]2)=[N:31][C:32]=1[NH2:33].C(N(CC)CC)C>C(O)C.C(O)(=O)C>[Si:1]([O:8][C:9]1([C:12]2[N:17]=[C:16]([C:18]3[NH:33][C:32]4=[N:31][C:30]([N:34]5[CH2:39][CH2:38][CH2:37][C@@H:36]([C:40]([N:42]6[CH2:43][CH2:44][CH2:45][CH2:46]6)=[O:41])[CH2:35]5)=[CH:29][CH:28]=[C:27]4[N:19]=3)[CH:15]=[CH:14][CH:13]=2)[CH2:10][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2723922Sodium ethoxideHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochlorideHCID 89855358HCID 89855358, compound

Product 1

HCID 178455006HCID 178455006, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×

Procedure

To a solution of 6-(1-((tert-butyldimethylsilyl)oxy)cyclopropyl)picolinonitrile (45.0 mg, 0.164 mmol) in ethanol (0.3 mL) was added dropwise a solution of sodium ethoxide in ethanol (0.1 mL, 21 wt %, 0.2 mmol). The reaction mixture was stirred at room temperature for 50 min and then heated to 35° C. for 1.5 h. To the mixture was added (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (77.2 mg, 0.2 mmol), triethylamine (47 μL, 0.3 mmol) and acetic acid (47 μL). The reaction mixture was heated to 110° C. for 50 min. The solution was transferred to a microwave vial and it was heated to 145° C. for 20 min. The solvent was removed under reduced pressure to afford (R)-(1-(2-(6-(1-((tert-butyldimethylsilyl)oxy)cyclopropyl)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone. The material was used without further purification.

Workup

  1. temperatureheated to 35° C. for 1.5 h
  2. temperatureThe reaction mixture was heated to 110° C. for 50 min
  3. temperaturewas heated to 145° C. for 20 min
  4. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-318ea404bf7b495491d6b00392260c77
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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