Nitrogen → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclopropylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396372ノート

反応式

HRID 1396372 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]3[CH2:20][CH2:19]3)[N:13]=2)[CH:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].N#N>CN1CCCC1=O.CN(C1C=CN=CC=1)C>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:21][C@@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]2[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]2[CH2:20][CH2:19]2)[N:13]=1)(=[O:9])[NH2:10]

参加物

6

反応物 3

HCID 947NitrogenHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 866897336-Chloro-4-(6-cyclopropylpyridin-2-ylamino)pyridazine-3-carboxamide

生成物 1

HCID 86689734tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclopropylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
150 °C

実験手順

To a stirred solution of 6-chloro-4-(6-cyclopropylpyridin-2-ylamino) pyridazine-3-carboxamide (104 mg, 359 mmol) in N-methyl-2-pyrrolidinone (5 mL) was added DMAP (47 mg, 377 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (154 mg, 718 μmol). The mixture was heated to 150° C. for 1.5 days, then a stream of N2 was blown into the flask while heating at 140° C. to evaporate the volatile solvents. The residue obtained was then purified by chromatography (silica, 50 μm, 60 g, Analogix, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min) to afford tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclopropylpyridin-2-ylamino)pyridazin-3 ylamino)cyclohexylcarbamate (126 mg, containing some residual NMP) as a brown viscous oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 11.43 (br. s., 1H) 8.17 (br. s., 1H) 8.03 (br. s., 1H) 7.44 (br. s., 1H) 7.03 (br. s., 1H) 6.80 (br. s., 1H) 6.60 (br. s., 1H) 5.76 (br. s., 1H) 5.49 (br. s., 1H) 3.82 (br. s., 1H) 3.24 (br. s., 1H) 2.03 (br. s., 1H) 1.32-1.91 (m, 8H) 1.45 (s., 9H) 1.05 (d, J=16.62 Hz, 4H). LCMS (EI/CI) m/z: 468 [M+H]. This was used directly in the next step without further purification.

後処理

  1. temperaturewhile heating at 140° C.
  2. customto evaporate the volatile solvents
  3. customThe residue obtained
  4. customwas then purified by chromatography (silica, 50 μm, 60 g, Analogix, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min)

出典と根拠

ORDレコード
ord-f9f15931f2bb4dc6aede33dcf2fb1257
出典データセット
uspto-grants-2014_12
特許番号
US08901124B2

反応ノート

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