Diisopropylethylamine → Tert-butyl 4-(2-acetamido-1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423096ノート

反応式

HRID 423096 の反応式
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[C:25]([O:29][C:30]([NH:32][C:33]1([C:48]([OH:50])=O)[CH2:38][CH2:37][N:36]([C:39]2[C:40]3[CH:47]=[CH:46][NH:45][C:41]=3[N:42]=[CH:43][N:44]=2)[CH2:35][CH2:34]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(C(C)C)C(C)C)C.[NH2:60][CH:61]([C:67]1[CH:72]=[CH:71][C:70]([Cl:73])=[CH:69][CH:68]=1)[CH2:62][NH:63][C:64](=[O:66])[CH3:65]>CN1C(=O)CCC1>[C:64]([NH:63][CH2:62][CH:61]([NH:60][C:48]([C:33]1([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:34][CH2:35][N:36]([C:39]2[C:40]3[CH:47]=[CH:46][NH:45][C:41]=3[N:42]=[CH:43][N:44]=2)[CH2:37][CH2:38]1)=[O:50])[C:67]1[CH:68]=[CH:69][C:70]([Cl:73])=[CH:71][CH:72]=1)(=[O:66])[CH3:65]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57750302N-[2-amino-2-(4-chlorophenyl)ethyl]acetamide2 回HCID 577503944-((tert-Butoxycarbonyl)amino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2 回

生成物 1

HCID 57750392Tert-butyl 4-(2-acetamido-1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate収率 81.7%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (89 mg, 0.23 mmol) was added in one portion to a stirred solution of 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (80 mg, 0.22 mmol) and N-ethyldiisopropylamine (0.046 mL, 0.27 mmol) in NMP (3 mL). The mixture was treated with N-(2-amino-2-(4-chlorophenyl)ethyl)acetamide (Intermediate 83) (52 mg, 0.24 mmol). The solution was stirred for 65 hours at room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed twice with water. The organic solution was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica using gradient elution (1% methanol/DCM to 15% methanol/DCM). Product containing fractions were combined to give tert-butyl 4-(2-acetamido-1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (100 mg, 81%) as colourless solid.

後処理

  1. customThe mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed twice with water
  3. concentrationThe organic solution was concentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography on silica using gradient elution (1% methanol/DCM to 15% methanol/DCM)
  5. additionProduct containing fractions

出典と根拠

ORDレコード
ord-0f38c426c4a2451b9b7540025e164f2a
出典データセット
uspto-grants-2012_01
特許番号
US08101623B2

反応ノート

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