Lithium borohydride → 4-{[(3-Chloro-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile

HRID 251241Notes

Reaction equation

HRID 251241 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([C:10]#[N:11])[CH:7]=[CH:6][C:5]=1[CH2:12][N:13]([CH2:22][C:23]1[C:28]([Cl:29])=[CH:27][CH:26]=[CH:25][N:24]=1)[CH2:14][C:15]1[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][N:16]=1.[Li+].[BH4-]>CO>[Cl:29][C:28]1[C:23]([CH2:22][N:13]([CH2:12][C:5]2[CH:6]=[CH:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[CH2:3][OH:2])[CH2:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][N:16]=2)=[N:24][CH:25]=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 672717452-{[(3-Chloro-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-5-cyano-benzoic acid methyl ester

Product 1

HCID 672725354-{[(3-Chloro-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrileYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a cold (0° C.) solution of 2-{[(3-Chloro-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-5-cyano-benzoic acid methyl ester (0.314 g, 0.75 mmol) in MeOH (7 mL) was added LiBH4 (106 mg, 4.89 mmol) and the mixture was allowed to warm to room temperature overnight. The mixture was concentrated and the residue was partitioned between CH2Cl2 (25 mL) and 1.0 N NaOH (10 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH) provided 0.19 g (65%) of 4-{[(3-Chloro-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile as a white foam. The white foam from above (0.19 g, 0.48 mmol) was dissolved in NH3 saturated MeOH (10 mL), treated with Raney nickel (80 mg), and placed under 50 psi H2 on a Parr shaker, for 19 h. The mixture was filtered through celite and the cake was washed with methanol. The eluant was concentrated under reduced pressure. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 0.15 g (82%) of a 1:1 mixture of (5-aminomethyl-2-{[(3-chloro-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-phenyl)-methanol and (5-aminomethyl-2-{[(3-methyl-pyridin-2-ylmethyl)-pyridin-2-ylmethyl-amino]-methyl}-phenyl)-methanol as a white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 (25 mL) and 1.0 N NaOH (10 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2 (3×10 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-98f531f1d46847d689e79664c1abf480
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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