Dimethylacetamide → Diethyl 2-(4-(3,4-dibromophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate

HRID 511810

반응식

HRID 511810 반응식
C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:13]([O:15][P:16]([CH2:21][C:22]([OH:24])=O)([O:18][CH2:19][CH3:20])=[O:17])[CH3:14].[Br:25][C:26]1[CH:27]=[C:28]([NH:33][C:34]2[C:35]3[CH:43]=[C:42]([NH2:44])[N:41]=[CH:40][C:36]=3[N:37]=[CH:38][N:39]=2)[CH:29]=[CH:30][C:31]=1[Br:32].CC(N(C)C)=O>C1COCC1.O.ClCCl.CO>[Br:25][C:26]1[CH:27]=[C:28]([NH:33][C:34]2[C:35]3[CH:43]=[C:42]([NH:44][C:22](=[O:24])[CH2:21][P:16](=[O:17])([O:15][CH2:13][CH3:14])[O:18][CH2:19][CH3:20])[N:41]=[CH:40][C:36]=3[N:37]=[CH:38][N:39]=2)[CH:29]=[CH:30][C:31]=1[Br:32]

참가 물질

8

반응물 4

HCID 31374DimethylacetamideHCID 36704(Diethoxyphosphinyl)acetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 86668941N4-(3,4-dibromophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine

생성물 1

HCID 86668942Diethyl 2-(4-(3,4-dibromophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate수율 95.1%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회HCID 21226129Dichloromethane methanol용매

반응 조건

온도
40 °C

실험 절차

To a stirred mixture of CDI (2.74 g, 16.9 mmol) and dry THF (13 mL), at room temperature and under a nitrogen atmosphere, was added a solution of 2-(diethoxyphosphoryl)acetic acid (2.96 g, 15.1 mmol) in THF (10 mL). After addition the reaction mixture was stirred further at 40° C. (bath) for 15 min (whence evolution of gases ceased). A solution of compound 225 (2.38 g, 6.02 mmol) in a mixed solvents of dry THF (7 mL) and DMA (8 mL) was added and stirred further at 40° C. The reaction was monitored by TLC (dichloromethane-MeOH=15:1). After stirred for 4 h, the reaction mixture was poured into water (250 mL) and stirred with petroleum ether (350 mL) at room temperature for 20 min. Petroleum ether layer was decanted. It was repeated once more with petroleum ether (200 mL). The solid was collected by suction filtration; washed with water (5×30 mL) and dried to give diethyl 2-(4-(3,4-dibromophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate (234) (3.28 g, 95%); mp 120-124° C.; 1H NMR δ [(CD3)2SO]: 10.89 (s, 1H), 10.41 (s, 1H), 9.04 (s, 1H), 8.88 (s, 1H), 8.67 (s, 1 H), 8.34 (d, J=2.5 Hz, 1H), 7.87 (dd, J=8.8, 2.5 Hz, 1H), 7.77 (d, J=8.8 Hz, 1H), 4.17-4.03 (m, 4H), 3.32 (d, J=21.6 Hz, 2H), 1.26 (t, J=7.0 Hz, 6H). Anal. Calcd for C19H20Br2N5O4P: C, 39.81; H, 3.52; N, 12.22%. Found C, 39.48; H, 3.78; N, 11.79%.

후처리

  1. additionAfter addition the reaction mixture
  2. stirringstirred further at 40° C
  3. stirringAfter stirred for 4 h
  4. customPetroleum ether layer was decanted
  5. filtrationThe solid was collected by suction filtration
  6. washwashed with water (5×30 mL)
  7. customdried

출처 및 근거

ORD 기록
ord-4ee94104aa4542c889c2f277aa800e20
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09101632B2

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