Triethylamine → tert-butyl N-[4-[3-(4-methylpyrimidin-5-yl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

HRID 2216191ノート

反応式

HRID 2216191 の反応式
Br[C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[N:6][CH:7]=1.[C:9]([O:13][C:14](=[O:37])[NH:15][C:16]([C:18]1[S:19][C:20]([S:35][CH3:36])=[C:21]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[CH:27]=2)(=[O:25])=[O:24])[CH:22]=1)=[NH:17])([CH3:12])([CH3:11])[CH3:10].C([O-])([O-])=O.[Na+].[Na+].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.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.CCOC(C)=O.O1CCOCC1.C1(C)C=CC=CC=1.C(O)C>[C:9]([O:13][C:14](=[O:37])[NH:15][C:16](=[NH:17])[C:18]1[S:19][C:20]([S:35][CH3:36])=[C:21]([S:23]([C:26]2[CH:27]=[CH:28][CH:29]=[C:30]([C:2]3[C:3]([CH3:8])=[N:4][CH:5]=[N:6][CH:7]=3)[CH:31]=2)(=[O:25])=[O:24])[CH:22]=1)([CH3:12])([CH3:10])[CH3:11]

参加物

12

反応物 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 124618635-Bromo-4-methylpyrimidineHCID 140043492[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]boronic acid

生成物 1

HCID 145857624tert-butyl N-[4-[3-(4-methylpyrimidin-5-yl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate収率 87%

試薬・触媒・溶媒 6

HCID 178418397HCID 178418397、化合物触媒HCID 178418476HCID 178418476、化合物触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a flask with a reflux condenser under argon was added 5-Bromo-4-methyl-pyrimidine (9 mg, 0.044 mmol), prepared according to the procedure of Yamanaka, Sakamoto, Nishimura, and Sagi, Chem. Pharm. Bull. 35(8), 3119–3126 (1987). {[4-(3-dihydroxyboranyl-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (20 mg, 0.044 mmol, Example 140: step a), Na2CO3 (2M, 0.220 mL, 0.44 mmol), Pd(PPh3)4 (8 mg, 0.007 mmol), ethanol (0.220 mL) and toluene (0.440 mL). PdCl2(PPh3)2 (42 mg, 0.06 mmol), dioxane (4 mL), and triethylamine (420 μL, 3 mmol) and the mixture was stirred for 2 h 15 min at 90° C. After cooling to rt, EtOAc (2 mL) and NaHCO3 (saturated, 2 mL) were added and the layers were separated. The organic layer concentrated in vacuo followed by purification of the crude material by preparative TLC (5% methanol in dichloromethane) to yield the title compound (19 mg, 87%) as a white solid. 1H-NMR (CDCl3): δ 9.12 (s, 1H), 8.54 (s, 1H), 8.10–7.29 (m, 7H), 2.59 (s, 3H), 2.50 (s, 3H), 1.51 (s, 9H). ESI-MS (m/z): Calcd. for C22H24N4O4S3: 504.1 (M−BOC)+H; found: 405.1.

後処理

  1. customprepared
  2. customthe layers were separated
  3. concentrationThe organic layer concentrated in vacuo
  4. customfollowed by purification of the crude material by preparative TLC (5% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-c8eede3438b94a79b08d74ddfdc49513
出典データセット
uspto-grants-2006_09
特許番号
US07109354B2

反応ノート

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