2-Bromopyrimidine → HCID 66833193, compound

HRID 2044065Notes

Reaction equation

HRID 2044065 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.Br[C:33]1[N:38]=[CH:37][CH:36]=[CH:35][N:34]=1.CCN(C(C)C)C(C)C>C1COCC1.C(OCC)(=O)C>[N:26]1([C:24]([C:21]2[CH:20]=[CH:19][C:18]([NH:17][C:10]3[N:9]=[C:8]([N:4]4[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][C:33]5[N:38]=[CH:37][CH:36]=[CH:35][N:34]=5)[CH2:3]4)[CH:16]=[CH:15][C:11]=3[C:12]([NH2:14])=[O:13])=[CH:23][CH:22]=2)=[O:25])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

6

Reactant 3

HCID 783452-BromopyrimidineHCID 81531DiisopropylethylamineHCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 66833193HCID 66833193, compoundYield 30.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (50 mg, 0.118 mmol), 2-bromopyrimidine (22.47 mg, 0.141 mmol), and DIEA (0.041 mL, 0.236 mmol) in THF (1 mL) was stirred at 100° C. overnight. The reaction mixture was diluted with ethyl acetate, washed with water, 10% LiCl, and concentrated. The residue was purified by prep-HPLC and the product containing fractions were collected, basified with 1N NaOH, extracted with CH2Cl2, washed with water, and concentrated to give 18 mg of (R)-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(3-(pyrimidin-2-ylamino)piperidin-1-yl)nicotinamide as a light yellow solid. LCMS: (M+H)+=503.23. 1H NMR (500 MHz, CDCl3) δ ppm 11.19 (1H, s), 8.27 (2H, d, J=4.58 Hz), 7.68 (2H, d, J=8.71 Hz), 7.51 (1H, d, J=8.71 Hz), 7.27 (2H, d, J=8.71 Hz), 6.56 (1H, t, J=4.81 Hz), 6.12 (1H, d, J=9.16 Hz), 5.57 (2H, br. s.), 5.26 (1H, d, J=7.79 Hz), 4.20 (1H, dd, J=12.83, 3.21 Hz), 4.09 (1H, dt, J=7.79, 3.89 Hz), 3.89-3.98 (1H, m), 3.49-3.83 (8H, m), 3.42-3.48 (1H, m), 3.39 (1H, dd, J=12.83, 7.79 Hz), 2.04-2.13 (2H, m), 1.69-1.92 (2H, m).

Workup

  1. washwashed with water, 10% LiCl
  2. concentrationconcentrated
  3. customThe residue was purified by prep-HPLC and the product
  4. additioncontaining fractions
  5. customwere collected
  6. extractionextracted with CH2Cl2
  7. washwashed with water
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1ff7e0308ecd486aa1b85e3d0a6ec27e
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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