Potassium Iodide → 2-{[(4-tert-Butoxycarbonylamino-butyl)-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

HRID 1624317ノート

反応式

HRID 1624317 の反応式
[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][NH:12][CH:13]1[C:18]2=[N:19][CH:20]=[CH:21][CH:22]=[C:17]2[O:16][CH2:15][CH2:14]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[C:33]([O:37][C:38]([N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[C:41]1[CH2:49]Cl)=[O:39])([CH3:36])([CH3:35])[CH3:34].[I-].[K+]>CC#N>[C:33]([O:37][C:38]([N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[C:41]1[CH2:49][N:12]([CH2:11][CH2:10][CH2:9][CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:23])[CH:13]1[C:18]2=[N:19][CH:20]=[CH:21][CH:22]=[C:17]2[O:16][CH2:15][CH2:14]1)=[O:39])([CH3:36])([CH3:35])[CH3:34]

参加物

6

反応物 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 69296245[4-(3,4-Dihydro-2H-pyrano[3,2-b]pyridin-4-ylamino)-butyl]-carbamic acid tert-butyl ester

生成物 1

HCID 691565352-{[(4-tert-Butoxycarbonylamino-butyl)-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester収率 67.5%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of [4-(3,4-Dihydro-2H-pyrano[3,2-b]pyridin-4-ylamino)-butyl]-carbamic acid tert-butyl ester (329 mg, 1.02 mmol) in CH3CN (5 mL) was added N,N-diisopropylethylamine (0.28 mL, 1.63 mmol) followed by 2-chloromethyl-benzimidazole-1-carboxylic acid tert-butyl ester (328 mg, 1.23 mmol) and potassium iodide (20 mg, 0.1 mmol). The resultant mixture was heated to 60° C. for 16 hours then cooled to room temperature. The mixture was concentrated and the residue was partitioned between CH2Cl2 (25 mL) and saturated aqueous NaHCO3 (20 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (2×15 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by flash column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 95:4:1) provided 2-{[(4-tert-Butoxycarbonylamino-butyl)-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester (380 mg, 67%) as a white foam.

後処理

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 (25 mL) and saturated aqueous NaHCO3 (20 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2 (2×15 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude material by flash column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 95:4:1)

出典と根拠

ORDレコード
ord-511fcc298fe440788d72aae6340bb6a8
出典データセット
uspto-grants-2014_07
特許番号
US08778967B2

反応ノート

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