Triethylamine → (R)-6-(3-(3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044041Notes

Reaction equation

HRID 2044041 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:20][CH:19]=3)[N:9]=2)[CH2:3]1.[CH:32]1([C:35]2[S:39][C:38]([NH:40][C:41](=O)[O:42]C3C=CC=CC=3)=[N:37][N:36]=2)[CH2:34][CH2:33]1.CCN(CC)CC>C(Cl)Cl>[CH:32]1([C:35]2[S:39][C:38]([NH:40][C:41](=[O:42])[NH:1][C@@H:2]3[CH2:7][CH2:6][CH2:5][N:4]([C:8]4[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]5[CH:19]=[CH:20][C:21]([C:24]([N:26]6[CH2:31][CH2:30][O:29][CH2:28][CH2:27]6)=[O:25])=[CH:22][CH:23]=5)[N:9]=4)[CH2:3]3)=[N:37][N:36]=2)[CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 19227158Phenyl 5-cyclopropyl-1,3,4-thiadiazol-2-ylcarbamateHCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 66833002(R)-6-(3-(3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 50.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (40 mg, 0.094 mmol), phenyl 5-cyclopropyl-1,3,4-thiadiazol-2-ylcarbamate (29.5 mg, 0.113 mmol), and Et3N (0.016 mL, 0.113 mmol) in CH2Cl2 (2 mL) was stirred at rt overnight. The reaction mixture was diluted with CH2Cl2, washed with water, and concentrated. The residue was purified by prep-HPLC. The product containing fractions were collected, neutralized with saturated NaHCO3, extracted with CH2Cl2, separated, and concentrated to give 28 mg of (R)-6-(3-(3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a light pink solid. LCMS: (M+H)+=592.18. 1H NMR (400 MHz, CDCl3-MIX) δ ppm 11.09 (1H, s), 7.59 (2H, d, J=8.79 Hz), 7.55 (1H, d, J=9.23 Hz), 7.24-7.28 (2H, m), 6.04 (1H, d, J=8.79 Hz), 3.93 (1H, dd, J=13.18, 3.08 Hz), 3.73-3.86 (2H, m), 3.53 (7H, d, J=6.15 Hz), 3.31-3.41 (1H, m), 3.22-3.31 (2H, m), 2.11-2.21 (1H, m), 1.90-2.00 (1H, m), 1.67-1.79 (1H, m), 1.51-1.65 (2H, m), 1.03-1.12 (2H, m), 0.89-0.96 (2H, m).

Workup

  1. washwashed with water
  2. concentrationconcentrated
  3. customThe residue was purified by prep-HPLC
  4. additionThe product containing fractions
  5. customwere collected
  6. extractionextracted with CH2Cl2
  7. customseparated
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9bcb5a8546de46cdbb76e4392eb14e3c
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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