Sodium Carbonate → tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 82394ノート

反応式

HRID 82394 の反応式
Cl.Cl.[F:3][C:4]1([F:20])[C:8]2[N:9]=[CH:10][N:11]=[C:12]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:7]=2[C@H:6]([CH3:19])[CH2:5]1.[C:21]([O:25][C:26]([N:28]([CH:41]([CH3:43])[CH3:42])[CH2:29][C@H:30]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)[C:31](O)=[O:32])=[O:27])([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CC(=O)OCC>[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([C@H:30]([C:31]([N:16]2[CH2:17][CH2:18][N:13]([C:12]3[C:7]4[C@H:6]([CH3:19])[CH2:5][C:4]([F:3])([F:20])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:14][CH2:15]2)=[O:32])[CH2:29][N:28]([CH:41]([CH3:42])[CH3:43])[C:26](=[O:27])[O:25][C:21]([CH3:23])([CH3:22])[CH3:24])=[CH:35][CH:36]=1

参加物

8

反応物 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 66846210(R)-7,7-difluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride

生成物 1

HCID 67338612tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate収率 68%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒2 回

実験手順

To a solution of (R)-7,7-difluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (0.015 g, 0.046 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.016 g, 0.046 mmol), and DIEA (0.024 ml, 0.14 mmol) in 1.7 mL DCM was added HBTU (0.017 g, 0.046 mmol). The reaction mixture was stirred 15 hours, after which 2M Na2CO3 was added. The mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 12S) by first flushing with about 120 mL 5:1 DCM:EA, then gradient to 1:1 DCM:EA to give tert-butyl(S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.018 g, 68% yield) as a white foam. MS (APCI)+ m/z 578 [M+H]+.

後処理

  1. extractionThe mixture was extracted with DCM
  2. dry with materialthe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude was purified on silica gel (Biotage 12S)
  6. customby first flushing with about 120 mL 5:1 DCM

出典と根拠

ORDレコード
ord-18e929e74b754b77b92396335656add8
出典データセット
uspto-grants-2014_09
特許番号
US08846681B2

反応ノート

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