4-Methylmorpholine → Ethyl 4,6-dimethylpyrimidine-5-carboxylate

HRID 970915Notes

Reaction equation

HRID 970915 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([CH3:11])[N:5]=[CH:4][N:3]=1.N[CH2:13][C:14]1C=C(C=CC=1)CN(CC1NC2C=CC=CC=2N=1)C1C2N=CC=CC=2CCC1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH2:13]([O:9][C:8]([C:7]1[C:2]([CH3:1])=[N:3][CH:4]=[N:5][C:6]=1[CH3:11])=[O:10])[CH3:14]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 9887073HCID 9887073, compoundHCID 149222224,6-Dimethylpyrimidine-5-carboxylic acid

Product 1

HCID 20619427Ethyl 4,6-dimethylpyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Using General Procedure F: A solution of 4,6-dimethyl-pyrimidine-5-carboxylic acid from above (prepared as described in patent application PCT/US00/11632) (42 mg, 0.28 mmol), (3-aminomethyl-benzyl)-(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (100 mg, 0.25 mmol), HOBT (38 mg, 0.28 mmol) and 4-methylmorpholine (40 μL, 0.38 mmol) in DMF (0.8 mL) was flushed with N2. EDCI (54 mg, 0.28 mmol) was added and the mixture was stirred at room temperature overnight. Purification of the colorless syrup (150 mg) by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:2:1) followed by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:2:1) afforded AMD11084 (80 mg, 60%) as a white foam. 1H NMR (CDCl3) δ 1.64-1.77 (m, 1H), 1.91-2.08 (m, 2H), 2.18-2.34 (m, 1H), 2.37 (s, 6H), 2.69-2.91 (m, 2H), 3.73 (s, 2H), 3.80 (d, 1H, J=16.5 Hz), 4.00 (d, 1H, J=16.5 Hz), 4.07-4.13 (m, 1H), 4.69 (d, 2H, J=5.7 Hz), 6.53 (t, 1H, J=5.7 Hz), 6.96-7.10 (m, 3H), 7.16-7.22 (m, 2H), 7.29-7.31 (m, 2H), 7.40-7.45 (m, 3H), 8.64 (d, 1H, J=3.6 Hz), 8.81 (s, 1H); 13C NMR (CDCl3) δ 21.71, 22.28, 24.38, 29.55, 44.29, 49.22, 55.11, 61.90, 111.12, 118.82, 121.68, 122.78, 127.32, 128.67, 129.09, 129.24, 130.48, 135.22, 137.66, 137.83, 140.30, 147.22, 156.42, 157.60,157.91, 163.43, 166.96. ES-MS m/z 532.4 (M+H). Anal. Calcd. for C32H33N7O.0.4CH2Cl2: C, 68.80; H, 6.02; N, 17.33. Found: C, 68.56; H, 6.09; N, 17.34.

Workup

  1. customwas flushed with N2
  2. customPurification of the colorless syrup (150 mg) by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:2:1)
  3. customafforded AMD11084 (80 mg, 60%) as a white foam

Sources & evidence

ORD record
ord-af3bc4362b8e45efb4f1e1142a0e50c8
Source dataset
uspto-grants-2007_12
Patent number
US07312234B2

Reaction notes

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