Ethylenediamine → 4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]-3-fluorobenzamide

HRID 2363288ノート

反応式

HRID 2363288 の反応式
[C:1]([CH2:3][C:4]1([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:31]=[CH:30][N:29](COCC[Si](C)(C)C)[C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:7][N:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][C:9]=2[F:17])[CH2:5]1)#[N:2].F[P-](F)(F)(F)(F)F.[N:47]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:51]2[CH:52]=C[CH:54]=[CH:55][C:50]=2N=N1.C1([C@@H](N)C)CC1.C(N(CC)CC)C.C([O-])(O)=O.[Na+].C(N)CN>C(Cl)Cl>[C:1]([CH2:3][C:4]1([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:31]=[CH:30][NH:29][C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:7][N:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH:47][C@H:51]([CH:50]3[CH2:55][CH2:54]3)[CH3:52])=[O:13])=[CH:10][C:9]=2[F:17])[CH2:5]1)#[N:2]

参加物

8

反応物 6

HCID 3301EthylenediamineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 7363995(S)-1-CyclopropylethylamineHCID 71143553HCID 71143553、化合物

生成物 1

HCID 711557954-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]-3-fluorobenzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 4-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-3-fluorobenzoic acid (20.0 mg, 0.0365 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (19 mg, 0.044 mmol) in dichloromethylene (1.0 mL) was added to a mixture of (1S)-1-cyclopropylethanamine (4.7 mg, 0.055 mmol) and triethylamine (15 μL, 0.11 mmol) in methylene chloride (0.6 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was worked up with aqueous NaHCO3, and extracted with dichloromethylene (2×2 mL). The combined organic layers were washed with water (1 mL), concentrated and dried under reduced pressure. The residue was treated with methylene chloride (1.3 mL) and trifluoroacetic acid (0.6 mL), and stirred at room temperature for 1.5 hours. The mixture was concentrated under reduced pressure. The residue was dissolved in methanol (1.3 mL). Ethylenediamine (0.086 mL, 1.3 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours, and purified by RP-HPLC (pH=10) (the conditions are already mention before the examples) to afford the desired product. LCMS (M+H)+: m/z=485.2.

後処理

  1. extractionextracted with dichloromethylene (2×2 mL)
  2. washThe combined organic layers were washed with water (1 mL)
  3. concentrationconcentrated
  4. customdried under reduced pressure
  5. additionThe residue was treated with methylene chloride (1.3 mL) and trifluoroacetic acid (0.6 mL)
  6. stirringstirred at room temperature for 1.5 hours
  7. concentrationThe mixture was concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in methanol (1.3 mL)
  9. stirringThe reaction mixture was stirred at room temperature for 2 hours
  10. custompurified by RP-HPLC (pH=10) (the conditions

出典と根拠

ORDレコード
ord-b3aea291054741c8a6253194f2e7fe43
出典データセット
uspto-grants-2014_04
特許番号
US08691807B2

反応ノート

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