Nitrogen → HCID 67272698, compound

HRID 251283Notes

Reaction equation

HRID 251283 reaction equation
[C:1]([O:5][C:6](=[O:29])[N:7]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH2:26])=[CH:21][C:20]=1[CH2:27][OH:28])[CH:8]1[C:17]2[N:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:30][C:31](OC(C)=O)=[O:32].CCN(CC)CC.N#N>C(Cl)Cl>[C:1]([O:5][C:6](=[O:29])[N:7]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH:26][C:31](=[O:32])[CH3:30])=[CH:21][C:20]=1[CH2:27][OH:28])[CH:8]1[C:17]2[N:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 947NitrogenHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 67273307HCID 67273307, compound

Product 1

HCID 67272698HCID 67272698, compoundYield 99.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-aminomethyl-2-hydroxymethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-carbamic acid tert-butyl ester (0.86 g, 2.17 mmol) dissolved in CH2Cl2 (15 mL) was added Ac2O (0.21 mL, 2.17 mmol) and Et3N (0.31 mL, 2.17 mmol). The solution was stirred for 30 minutes under a positive pressure of N2. The reaction mixture was quenched with saturated aqueous NaHCO3 (25 mL) and extracted with CH2Cl2 (2×25 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to afford [4-(acetylamino-methyl)-2-hydroxymethyl-benzyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-carbamic acid tert-butyl ester as a white solid (0.95 g, 99%). 1H NMR (CDCl3) δ 1.06 (s, 9H), 1.65 (m, 1H), 2.01 (m, 3H), 2.08 (m, 1H), 2.70 (m, 2H), 3.87 (d, 1H, J=15.0 Hz), 4.09 (m, 1H), 4.41 (d, 3H, J=6.0 Hz), 5.07 (d, 1H, J=12.0 Hz), 5.56 (d, 1H, J=12.0 Hz), 5.96 (m, 1H), 6.98 (m, 1H), 7.15 (s, 2H), 7.32 (d, 1H, J=6.0 Hz), 7.41 (s, 1H), 8.15 (d, 1H, J=3.0 Hz). Deprotection with TFA following General Procedure F gave N-{3-hydroxymethyl-4-{(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl}-benzyl}-acetamide as an off-white solid. 1H NMR (CDCl3) δ 1.79 (m, 2H), 1.94 (m, 1H), 2.00 (s, 3H), 2.26 (m, 1H), 2.77 (m, 2H), 3.89 (m, 2H), 4.13 (d, 1H, J=12.0 Hz), 4.41 (m, 3H), 4.79 (d, 1H, J=12.0 Hz), 7.05 (m, 1H), 7.20 (m, 1H), 7.31 (m, 1H), 7.40 (m, 2H), 8.33 (d, 1H, J=3.0 Hz).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3 (25 mL)
  2. extractionextracted with CH2Cl2 (2×25 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-529e931105e9445786a2c1ebc512e17e
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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