Diisopropylethylamine → tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate

HRID 1842608ノート

反応式

HRID 1842608 の反応式
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:5]=[N:6][C:7]2[N:8]([N:10]=[CH:11][C:12]=2[C:13]2[CH:14]=[C:15]([C:19](O)=[O:20])[S:16][C:17]=2[CH3:18])[CH:9]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:50][C@H:51]1[C:56]([F:58])([F:57])[CH2:55][CH2:54][CH2:53][C@H:52]1[NH:59][C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:64])[CH3:63].C(N(C(C)C)CC)(C)C>CN(C=O)C.ClCCl>[C:62]([O:61][C:60](=[O:66])[NH:59][C@@H:52]1[CH2:53][CH2:54][CH2:55][C:56]([F:58])([F:57])[C@@H:51]1[NH:50][C:19]([C:15]1[S:16][C:17]([CH3:18])=[C:13]([C:12]2[CH:11]=[N:10][N:8]3[CH:9]=[C:4]([O:3][CH:2]([F:1])[F:22])[CH:5]=[N:6][C:7]=23)[CH:14]=1)=[O:20])([CH3:65])([CH3:63])[CH3:64]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamateHCID 683051734-[6-(Difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylic acid

生成物 1

HCID 89750994tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate収率 68.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

4-[6-(Difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylic acid (0.768 g, 2.36 mmol) and BOP (3.13 g, 7.08 mmol) were dissolved in DMF (15.7 mL) and stirred at room temperature for 5 min. To the reaction solution was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (0.650 g, 2.60 mmol) and diisopropylethyl amine (619, 3.54 mmol) and the reaction stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate twice and brine once. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-100% EtOAc/Hex) to give the title compound (0.900 g, 1.61 mmol). LRMS (APCI) calc'd for (C24H27F4N5O4S) [M+H]+, 558.2; found 558.0.

後処理

  1. stirringthe reaction stirred at room temperature for 16 h
  2. washwashed with saturated sodium bicarbonate twice
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (0-100% EtOAc/Hex)

出典と根拠

ORDレコード
ord-2597a562c507424a87e94c6f68fd807e
出典データセット
uspto-grants-2015_02
特許番号
US08946237B2

反応ノート

読み込み中…