Dichloromethane → (5-Aminomethyl-2-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol

HRID 251263Notes

Reaction equation

HRID 251263 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:30])[C:5]([CH2:8][N:9]([CH2:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=2[CH2:28][OH:29])[C:10]([CH3:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH3:11])=[N:6][CH:7]=1.[Li+].[BH4-].[OH-].[Na+].C(Cl)Cl>C1COCC1>[NH2:25][CH2:24][C:23]1[CH:26]=[CH:27][C:20]([CH2:19][N:9]([CH2:8][C:5]2[C:4]([CH3:30])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[C:10]([CH3:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH3:11])=[C:21]([CH2:28][OH:29])[CH:22]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 589971284-{[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile

Product 1

HCID 58997153(5-Aminomethyl-2-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanolYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile (0.5371 g, 1.2 mmol) in THF (12 mL) at 0° C. was added LiBH4 (0.2086 g, 9.6 mmol), then heated to 70° C. and stirred for 18 hours. 1N NaOH (25 mL) and CH2Cl2 (50 mL) were added and stirred for 10 minutes. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by column chromatography on silica gel (75:1:1 CH2Cl2-MeOH—NH4OH) provided 0.2330 g (48%) of COMPOUND 402 as a white solid. 1H NMR (CDCl3) δ 1.61 (s, 5H), 2.07 (s, 6H), 3.69 (s, 2H), 3.73 (s, 2H), 3.91 (s, 2H), 4.55 (s, 2H), 6.69-6.78 (bs, 1H), 6.94-6.97 (m, 1H), 7.02-7.08 (m, 3H), 7.21 (d, 1H, J=1.5 Hz), 7.49-7.55 (m, 1H), 7.77 (d, 1H, J=8.1 Hz), 8.05 (d, 1H, J=2.1 Hz), 8.45-8.48 (m, 1H). 13C NMR (CDCl3) δ 18.71, 24.43, 46.39, 51.43, 53.95, 63.49, 64.78, 122.10, 123.09, 126.25, 129.32, 130.26, 131.30, 132.25, 136.21, 137.16, 137.26, 141.33, 143.29, 144.59, 147.94, 156.80, 165.90. ES-MS m/z 425.4 (M+H). Anal. Calcd. for C24H29N4ClO.0.3H2O: C, 66.98; H, 6.93; N, 13.02; Cl, 8.24. Found: C, 67.11; H, 6.54; N, 12.13; Cl, 8.99.

Workup

  1. stirringstirred for 10 minutes
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with CH2Cl2 (3×50 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (75:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-01291c2901754d7b82a833911d56cc62
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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