Cyclopropylamine → 9-cyclopropyl-N-(cyclopropylmethyl)-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamide

HRID 528024ノート

反応式

HRID 528024 の反応式
[CH3:1][N:2]1[C:10]([C:11]([NH:13][CH2:14][CH:15]2[CH2:17][CH2:16]2)=[O:12])=[N:9][C:8]2[C:3]1=[N:4][CH:5]=[N:6][C:7]=2[N:18]1[CH2:23][CH2:22][CH:21]([N:24]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[NH:26][C:25]2=[O:33])[CH2:20][CH2:19]1.[CH:34]1(N2C(C(O)=O)=NC3C2=NC=NC=3N2CCC(N3C4C=CC=CC=4NC3=O)CC2)C[CH2:35]1.C1(N)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[CH:1]1([N:2]2[C:10]([C:11]([NH:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)=[O:12])=[N:9][C:8]3[C:3]2=[N:4][CH:5]=[N:6][C:7]=3[N:18]2[CH2:23][CH2:22][CH:21]([N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[NH:26][C:25]3=[O:33])[CH2:20][CH2:19]2)[CH2:35][CH2:34]1

参加物

7

反応物 5

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 569482049-methyl-N-(cyclopropylmethyl)-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamideHCID 66799957HCID 66799957、化合物

生成物 1

HCID 668023599-cyclopropyl-N-(cyclopropylmethyl)-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamide

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

9-Cyclopropyl-N-(cyclopropylmethyl)-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamide was prepared in the same manner as 9-methyl-N-(cyclopropylmethyl)-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamide. The 9-cyclopropyl-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxylic acid (0.09 g, 0.21 mmol) was treated with cycloproplyamine (0.305 g, 0.429 g mmol, 0.037 mL), HATU (0.163 g, 0.429 mmol), diisopropylethylamine (0.110 g, 0.858 mmol, 0.149 mL) and DMA (8 mL) at room temperature for 18 hours. Purification by preparative reverse phase HPLC (eluting with 0.01% aqueous ammonium acetate and acetonitrile) yielded 0.057 g of 9-cyclopropyl-N-(cyclopropylmethyl)-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamide as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.50 (broad s, 1H), 8.63 (t, 1H), 8.07 (s, 1H), 6.98 (m, 1H), 6.6.716 (m, 3H), 5.11 (broad s, 2H), 4.30 (m, 1H), 3.38 (m, 1H), 3.13 (dd, 1H), 2.93 (t,4H), 2.07 (t, 2H), 1.63 (m, 2H), 0.83 (m, 4H), 0.18 (m, 2H), 0.02 (m, 2H).MS (EI) for C25H28N8O2: 473 (MH+).

後処理

  1. customPurification
  2. washby preparative reverse phase HPLC (eluting with 0.01% aqueous ammonium acetate and acetonitrile)

出典と根拠

ORDレコード
ord-339800cc9f1a4ce198d8901aa7f13ac7
出典データセット
uspto-grants-2016_05
特許番号
US09346807B2

反応ノート

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