Hydrochloric Acid → Hydrochloric Acid

HRID 513266Notes

Reaction equation

HRID 513266 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=[C:8]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH:7]=1.[ClH:32].CCN(C(C)C)C(C)C.[C:42]([CH2:44][C:45](O)=[O:46])#[N:43].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN1C(=O)CCC1>[C:42]([CH2:44][C:45]([N:25]1[CH2:26][CH2:27][CH:22]([C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:8]3[CH:7]=[C:6]([NH:5][CH2:4][C:3]4[CH:28]=[CH:29][CH:30]=[CH:31][C:2]=4[F:1])[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=3)=[CH:21][CH:20]=2)[CH2:23][CH2:24]1)=[O:46])#[N:43].[ClH:32]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 56970645HCID 56970645, compound

Product 2

HCID 313Hydrochloric AcidHCID 67502299HCID 67502299, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Compound 4-(2-fluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 106) HCl salt (100 mg, 0.2 mmol) was stirred in 5 mL NMP. To the solution were added DIEA (0.35 mL, 2.0 mmol), cyanoacetic acid (85 mg, 1.0 mmol) and BOP (379 mg, 1.0 mmol). The mixture was stirred at RT for 3 h and quenched with TFA. The mixture was concentrated in vacuo and subjected to reverse phase prep HPLC to isolate the title compound as HCl salt. UV=259 nm. M+H found for C27H27FN6O2: 487.5. NMR (CD3OD): 8.03 (1H, s), 7.27 (1H, m), 7.24 (2H, d, J=8.4 Hz), 7.19 (1H, m), 7.09 (1H, m), 7.07-7.00 (3H, m), 5.78 (1H, s), 4.56 (1H, m), 4.41 (2H, s), 3.88 (1H, d, J=18.8 Hz), 3.83 (1H, m), 3.78 (1H, d, J=18.4 Hz), 3.17 (1H, m), 2.80 (1H, m), 2.72 (1H, m), 1.83 (2H, m), 1.61 (2H, m) ppm.

Workup

  1. customquenched with TFA
  2. concentrationThe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-54192c6bfc4f42fb8fad9c84fb0433a9
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Reaction notes

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