N,N-Dimethylglycine hydrochloride → 4-(2,3-Difluorobenzylamino)-6-(4-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)phenylamino)nicotinamide

HRID 513303ノート

反応式

HRID 513303 の反応式
[F:1][C:2]1[C:31]([F:32])=[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.Cl.[CH3:34][N:35]([CH3:40])[CH2:36][C:37](O)=[O:38].CCN(C(C)C)C(C)C.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>[F:1][C:2]1[C:31]([F:32])=[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:17]=[CH:18][C:19]([CH:22]3[CH2:23][CH2:24][N:25]([C:37](=[O:38])[CH2:36][N:35]([CH3:40])[CH3:34])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

参加物

6

反応物 4

HCID 75605N,N-Dimethylglycine hydrochlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

生成物 1

HCID 675026674-(2,3-Difluorobenzylamino)-6-(4-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)phenylamino)nicotinamide収率 76.5%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

The mixture of compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (50 mg, 0.11 mmol), N,N-dimethylglycine hydrochloride (31 mg, 0.22 mmol), DIEA (180 μL, 1.1 mmol) in 4 mL NMP was stirred at RT. To it was added BOP (210 mg, 0.55 mmol). The mixture was stirred for overnight, quenched with TFA, and subjected to reverse phase preparative HPLC to isolate the title compound (44 mg). MS found for C28H32F2N6O2 as (M+H)+ 523.5. UV: λ=259 nm. 1H NMR: (CD3OD) δ 8.17 (1H, s), 7.33 (2H, d, J=8.8 Hz), 7.26 (1H, m), 7.17 (1H, m), 7.14-7.07 (3H, m), 5.80 (1H, s), 4.68 (1H, m), 4.55 (2H, s), 4.37 (1H, d, J=16.0 Hz), 4.27 (1H, d, J=16.0 Hz), 3.81 (1H, m), 3.27 (1H, m), 2.97 (6H, s), 2.92-2.83 (2H, m), 1.95 (2H, m), 1.71 (2H, m) ppm.

後処理

  1. stirringThe mixture was stirred for overnight
  2. customquenched with TFA

出典と根拠

ORDレコード
ord-a4f7fe742d04418ca556ec0e13d556c1
出典データセット
uspto-grants-2015_08
特許番号
US09102625B2

反応ノート

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