N,N-Diethyl-2-propanamine → 2-Pyridin-3-yl-pyrimidine-5-carboxylic acid (5-methanesulfonyl-indol-1-yl)-amide

HRID 2382002Notes

Reaction equation

HRID 2382002 reaction equation
[CH2:1]([N:3](CC)C(C)C)C.Cl.N1C=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[N:21]=[CH:20][C:19]([C:22]([OH:24])=O)=[CH:18][N:17]=1.[CH3:25][S:26]([C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[N:34]([NH2:38])[CH:33]=[CH:32]2)(=[O:28])=[O:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[CH3:25][S:26]([C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[N:34]([NH:38][C:22]([C:19]1[CH:20]=[N:21][C:16]([C:11]3[CH:1]=[N:3][CH:14]=[CH:13][CH:12]=3)=[N:17][CH:18]=1)=[O:24])[CH:33]=[CH:32]2)(=[O:28])=[O:27]

Participants

6

Reactant 4

HCID 521913N,N-Diethyl-2-propanamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 685530312-Pyridin-2-yl-pyrimidine-5-carboxylic acid hydrochlorideHCID 685555925-Methanesulfonyl-indol-1-ylamine

Product 1

HCID 250993552-Pyridin-3-yl-pyrimidine-5-carboxylic acid (5-methanesulfonyl-indol-1-yl)-amideYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Diethyl-iso-propylamine (3.84 mmol) is added a solution of 2-pyridin-2-yl-pyrimidine-5-carboxylic acid hydrochloride (1.28 mmol), 5-methanesulfonyl-indol-1-ylamine (1.28 mmol) and TBTU (1.92 mmol) in anhydrous DMF (16 mL) at rt. The reaction mixture is stirred at 90° C. overnight and then concentrated in vacuo. The residue is dissolved in EtOAc (60 mL), and washed with water (2×30 mL) and brine (20 mL), The organic layer is separated, washed with water (2×20 mL) and brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0-5% MeOH in DCM to afford 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (5-methanesulfonyl-indol-1-yl)-amide (125 mg, 25%) as a solid. MS: 394 (M+H); 1H NMR (300 MHz, CDCl3): δ 3.10 (s, 3H), 6.61 (m, H) 6.98 (m, H), 7.34 (s, H), 7.51 (m, H), 7.91 (s, H), 8.83 (m, 2H), 9.49 (s, H), 9.77 (s, H), 10.10 (s, N—H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue is dissolved in EtOAc (60 mL)
  3. washwashed with water (2×30 mL) and brine (20 mL)
  4. customThe organic layer is separated
  5. washwashed with water (2×20 mL) and brine (20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-19f1a34ffeaa4544a7afbdb6c5983738
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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