Triphenylphosphine → Diethyl N-[4-[(2,4-diaminopyrido[2,3-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate

HRID 370522

反応式

HRID 370522 の反応式
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrBr.[NH2:22][C:23]1[N:24]=[C:25]([NH2:35])[C:26]2[CH:32]=[C:31]([CH2:33]O)[CH:30]=[N:29][C:27]=2[N:28]=1.[NH2:36][C:37]1[CH:58]=[CH:57][C:40]([C:41]([NH:43][C@H:44]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:45][CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])=[O:42])=[CH:39][CH:38]=1>CC(N(C)C)=O>[NH2:22][C:23]1[N:24]=[C:25]([NH2:35])[C:26]2[CH:32]=[C:31]([CH2:33][NH:36][C:37]3[CH:38]=[CH:39][C:40]([C:41]([NH:43][C@H:44]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:45][CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])=[O:42])=[CH:57][CH:58]=3)[CH:30]=[N:29][C:27]=2[N:28]=1

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 24408BromineHCID 73002Diethyl N-(4-aminobenzoyl)-L-glutamateHCID 4874162,4-Diamino-6-(hydroxymethyl)pyrido[2,3-d]pyrimidine

生成物 1

HCID 12908481Diethyl N-[4-[(2,4-diaminopyrido[2,3-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
0 °C

実験手順

A solution of triphenylphosphine (430 mg, 1.64 mmol) in anhydrous DMAC (4 ml) at 0° C. was treated dropwise under N2 with bromine (84 μL, 1.64 mmol). The solution was stirred at 0° C. for 15 minutes, treated with the compound obtained in Example 2 (100 mg, 0.76 mmol), and stirred at 25° C. for 1.7 hours to give the compound of Formula IIIA. This solution was treated with diethyl p-aminobenzoyl-L-glutamate (194 mg, 0.603 mmol), stirred at 25° C. for 17 hours and poured into ice water (40 ml). The resulting solution (pH 2) was filtered to remove triphenylphosphine oxide, adjusted to pH 6.8 with 50% NaOH, and cooled in an ice bath. The precipitate of crude product (VII; R=H, R1 =C2H5) was collected by centrifugation, washed with H2O and dried in vacuo (P2O5); yield 136 mg (73%). The retention time (HPLC) and rf value (TLC) of this product were identical to those obtained from the analytical sample obtained in Part A of this example. Mass spectrum: m/e 496 (M+1)+.

後処理

  1. stirringstirred at 25° C. for 1.7 hours
  2. customto give the compound of Formula IIIA
  3. stirringstirred at 25° C. for 17 hours
  4. filtrationThe resulting solution (pH 2) was filtered
  5. customto remove triphenylphosphine oxide
  6. temperaturecooled in an ice bath
  7. customThe precipitate of crude product (VII; R=H, R1 =C2H5) was collected by centrifugation
  8. washwashed with H2O
  9. dry with materialdried in vacuo (P2O5)
  10. customthose obtained from the analytical sample

出典と根拠

ORDレコード
ord-fbcac3e64fe642baba4a087245e81abd
出典データセット
uspto-grants-1985_07
特許番号
US04526964

関連ノート

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