Ammonia → HCID 71483937, compound

HRID 2409939Notes

Reaction equation

HRID 2409939 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]3[CH:28]=[C:27](/[CH:29]=[CH:30]\[C:31](O)=[O:32])[CH:26]=[CH:25][N:24]=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].CC[N:36](CC)CC.ClC(OCC(C)C)=O.N>CO.C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]3[CH:28]=[C:27](/[CH:29]=[CH:30]\[C:31]([NH2:36])=[O:32])[CH:26]=[CH:25][N:24]=3)[CH2:10]2)=[CH:7][CH:8]=1)#[N:2]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 71227046HCID 71227046, compound

Product 1

HCID 71483937HCID 71483937, compoundYield 22.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottom flask was added (Z)-3-(2-(((1R,2R)-2-(((S)-1-(4-cyanophenyl)piperidin-3-yl)amino)cyclohexyl)amino)pyridin-4-yl)acrylic acid (35 mg, 0.063 mmol), THF (0.8 mL) and Et3N (0.026 mL, 0.188 mmol). The reaction was cooled to 0° C. Then isobutyl chloroformate (9.04 μl, 0.069 mmol) was added to the reaction and the reaction was stirred at 0° C. for 15 mins before ammonia (0.045 mL, 0.313 mmol) in methanol was added to the reaction. The reaction was stirred at 0° C. for 30 mins. The reaction was concentrated and purified using RP prep-HPLC. The desired fraction was concentrated to give (Z)-3-(2-(((1R,2R)-2-(((S)-1-(4-cyanophenyl)piperidin-3-yl)amino)cyclohexyl)amino)pyridin-4-yl)acrylamide (8 mg, 0.014 mmol, 21.98% yield) as a light brown film. Anal. Calcd. for C26H32N6O m/z 444.3, found: 445.5 (M+H)+; 1H NMR (400 MHz, METHANOL-D4) δ ppm 7.87 (d, J=6.6 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.00-6.89 (m, 3H), 6.84 (br. s., 1H), 6.67 (d, J=12.6 Hz, 1H), 6.35 (d, J=12.6 Hz, 1H), 3.88-3.67 (m, 2H), 3.63-3.52 (m, 1H), 3.50-3.42 (m, 1H), 3.40-3.33 (m, 2H), 3.18-3.08 (m, 1H), 2.34 (d, J=12.6 Hz, 1H), 2.14 (dd, J=9.6, 3.0 Hz, 2H), 1.91-1.72 (m, 4H), 1.66-1.53 (m, 1H), 1.52-1.40 (m, 3H), 1.33-1.26 (m, 1H)

Workup

  1. additionwas added to the reaction
  2. concentrationThe reaction was concentrated
  3. custompurified
  4. concentrationThe desired fraction was concentrated

Sources & evidence

ORD record
ord-dd48fb4147bd48cda20ed07f75e7956e
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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