Triethylamine → 5-[3,3-Dimethyl-4-(tetrahydro-furan-3-yloxy)-but-1-ynyl]-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 1046446ノート

反応式

HRID 1046446 の反応式
[CH3:1][C:2]([CH3:12])([C:10]#[CH:11])[CH2:3][O:4][CH:5]1[CH2:9][CH2:8][O:7][CH2:6]1.[CH3:13][O:14][C:15]([C:17]1[S:18][C:19](I)=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:37][CH2:36][CH:35]([OH:38])[CH2:34][CH2:33]1)[C:23]([CH:25]1[CH2:30][CH2:29][CH:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])=[O:16].C(N(CC)CC)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:11]#[C:10][C:2]([CH3:12])([CH3:1])[CH2:3][O:4][CH:5]2[CH2:9][CH2:8][O:7][CH2:6]2)=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:33][CH2:34][CH:35]([OH:38])[CH2:36][CH2:37]1)[C:23]([CH:25]1[CH2:30][CH2:29][CH:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])=[O:16]

参加物

7

反応物 3

HCID 8471TriethylamineHCID 249893473-[(4-Hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxHCID 581138943-(2,2-Dimethyl-but-3-ynyloxy)-tetrahydro-furan

生成物 1

HCID 581141645-[3,3-Dimethyl-4-(tetrahydro-furan-3-yloxy)-but-1-ynyl]-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester収率 75.8%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 3-(2,2-dimethyl-but-3-ynyloxy)-tetrahydro-furan (169 mg, 1.00 mmol), 3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (404 mg, 0.80 mmol) and triethylamine (1.2 mL, 8.61 mmol) in DMF (1.2 mL) was degassed for 10 minutes with nitrogen. PdCl2(PPh3)2 (25 mg, 0.036 mmol) and CuI (6.0 mg, 0.031 mmol) was added and the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction was placed in a 65° C. oil bath and heated for 2.5 h. The reaction was cooled and partitioned between ethyl acetate and sat. NaHCO3. The organic layer was separated, washed with 5% LiCl, brine, dried over Na2SO4 and concentrated to give a dark brown foam. Purification by flash column chromatography on silica gel using 50% ethyl acetate in hexanes then 5% methanol in ethyl acetate provided 5-[3,3-dimethyl-4-(tetrahydro-furan-3-yloxy)-but-1-ynyl]-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (331 mg, 75%) as a pale yellow foam.

後処理

  1. customthe resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
  2. customwas placed in a 65° C.
  3. temperatureheated for 2.5 h
  4. temperatureThe reaction was cooled
  5. custompartitioned between ethyl acetate and sat. NaHCO3
  6. customThe organic layer was separated
  7. washwashed with 5% LiCl, brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customto give a dark brown foam
  11. customPurification by flash column chromatography on silica gel using 50% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-c45a278d4ef94792b7101171a4e22211
出典データセット
uspto-grants-2013_10
特許番号
US08569302B2

反応ノート

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