Triethylamine → tert-butyl 3-((2-amino-6-((R)-3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)carbamoyl)piperidine-1-carboxylate

HRID 931190Notes

Reaction equation

HRID 931190 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([C:15]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)=[O:16])[CH2:10]2)=[N:6][C:7]=1[NH2:8].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][C@@H:31]([C:35](O)=[O:36])[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(N(CC)CC)C>O1CCOCC1>[NH2:8][C:7]1[C:2]([NH:1][C:35]([CH:31]2[CH2:32][CH2:33][CH2:34][N:29]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:30]2)=[O:36])=[CH:3][CH:4]=[C:5]([N:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([C:15]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)=[O:16])[CH2:10]2)[N:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylateHCID 89854052(R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

Product 1

HCID 117966487tert-butyl 3-((2-amino-6-((R)-3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)carbamoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (3.60 mmol) in 1,4-dioxane (20 mL) was added (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (3.60 mmol), 1-Propanephosphonic acid cyclic anhydride (10.8 mmol), and triethylamine (32.4 mmol). The reaction mixture was stirred at room temperature for 16 h. The solvent was removed under reduced pressure and a solution of methanol/dichloromethane (1:9, 50 mL) was added followed by a saturated aqueous solution of sodium bicarbonate (50 mL), and the layers were separated. The aqueous layer was extracted again with methanol/dichloromethane (1:9, 25 mL) and the combined organics were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford tert-butyl 3-((2-amino-6-((R)-3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)carbamoyl)piperidine-1-carboxylate which was used without further purification.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additiona solution of methanol/dichloromethane (1:9, 50 mL) was added
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted again with methanol/dichloromethane (1:9, 25 mL)
  5. dry with materialthe combined organics were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fcc325980c7c449388edfbb16b6e8506
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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