Triethylamine → 5-Bromo-3-[(3-morpholin-4-yl-propylamino)methyl]pyridin-2-ylamine

HRID 1362111Notes

Reaction equation

HRID 1362111 reaction equation
Br.[NH2:2][C:3]1[C:8]([CH:9]=O)=[CH:7][C:6]([Br:11])=[CH:5][N:4]=1.C(N(CC)CC)C.[NH2:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.[BH4-].[Na+]>CO>[Br:11][C:6]1[CH:7]=[C:8]([CH2:9][NH:19][CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:3]([NH2:2])=[N:4][CH:5]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 61055N-(3-Aminopropyl)morpholine2×HCID 4311764Sodium borohydrideHCID 866061462-Amino-5-bromonicotinaldehyde hydrobromide

Product 1

HCID 594569475-Bromo-3-[(3-morpholin-4-yl-propylamino)methyl]pyridin-2-ylamineYield 54%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-amino-5-bromo-pyridine-3-carbaldehyde hydrobromide (4.30 g, 15.3 mmol) in MeOH (100 mL) was added triethylamine (4.3 mL, 31 mmol) and the mixture was stirred at room temperature for 10 min. The resulting suspension was treated with 4-(3-aminopropyl)morpholine (2.5 mL, 17 mmol) and the mixture was stirred for 7 h. TLC analysis indicated remaining starting material. Additional 4-(3-aminopropyl)morpholine (1.0 mL, 6.8 mmol) was added, and the mixture was allowed to stir overnight at room temperature. The mixture was cooled and then NaBH4 (0.87 g, 23.0 mmol) was added in two portions. The mixture was stirred at room temperature for 4 h. The solvent was removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH/Et3N, 97/2.5/0.5 to 85/14.5/0.5) gave the title compound (2.70 g, 54%) as a brown oil: MS (ESI) m/e 329 (M+H)+.

Workup

  1. stirringthe mixture was stirred for 7 h
  2. stirringto stir overnight at room temperature
  3. temperatureThe mixture was cooled
  4. stirringThe mixture was stirred at room temperature for 4 h
  5. customThe solvent was removed in vacuo
  6. customPurification by column chromatography (silica gel, CH2Cl2/MeOH/Et3N, 97/2.5/0.5 to 85/14.5/0.5)

Sources & evidence

ORD record
ord-1631858270a5415c8ff9059ae98f209b
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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