3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → tert-butyl 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-cyano-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]azetidine-1-carboxylate

HRID 626844ノート

反応式

HRID 626844 の反応式
Cl.Cl.[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH:14]([C:16]3[CH:17]=[C:18]([Cl:29])[C:19]([C:27]#[N:28])=[C:20]4[C:26]=3[O:25][CH2:24][CH2:23][NH:22][CH2:21]4)[CH3:15])[N:11]=[C:12]([CH3:13])[C:5]=12.O=[C:31]1[CH2:34][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:32]1.C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C>[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH:14]([C:16]3[C:26]4[O:25][CH2:24][CH2:23][N:22]([CH:31]5[CH2:32][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:34]5)[CH2:21][C:20]=4[C:19]([C:27]#[N:28])=[C:18]([Cl:29])[CH:17]=3)[CH3:15])[N:11]=[C:12]([CH3:13])[C:5]=12

参加物

6

反応物 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5003444Sodium cyanoborohydrideHCID 866975369-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile bishydrochloride

生成物 1

HCID 86697538tert-butyl 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-cyano-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]azetidine-1-carboxylate収率 35.7%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile bishydrochloride (0.030 g, 0.078 mmol) was dissolved in methanol (3.0 mL), and the tert-butyl 3-oxoazetidine-1-carboxylate (0.027 g, 0.16 mmol) and then sodium cyanoborohydride (0.0098 g, 0.16 mmol) were added. The reaction was heated to 60° C. for 3 hrs and then allowed to cool to room temperature. The reaction was diluted with ethyl acetate and washed with brine. The organic layer dried over magnesium sulfate and concentrated to give the crude product as an amber oil. The oil was purified by prep HPLC on a C-18 column eluting water:acetonitrile gradient at pH 10 to give tert-butyl 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-cyano-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]azetidine-1-carboxylate (0.015 g, 35%). LCMS calculated for C26H32ClN8O3 (M+H)+: m/z=539.2; found: 539.2.

後処理

  1. temperatureto cool to room temperature
  2. washwashed with brine
  3. dry with materialThe organic layer dried over magnesium sulfate
  4. concentrationconcentrated
  5. customto give the crude product as an amber oil
  6. customThe oil was purified by prep HPLC on a C-18 column
  7. washeluting water

出典と根拠

ORDレコード
ord-0a631bac2b7d4f02bc4338127c1a9517
出典データセット
uspto-grants-2016_04
特許番号
US09309251B2

反応ノート

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