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Sodium Carbonate → 5-(7-Tert-butyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine

HRID 528480
ノート
印刷プレビュー

反応式

HRID 528480 の反応式
[C:1]([CH:5]1[O:21][C:9]2[N:10]=[C:11](Cl)[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:8]=2[O:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.C(#N)C>[C:1]([CH:5]1[O:21][C:9]2[N:10]=[C:11]([C:30]3[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=3)[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:8]=2[O:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 867117617-tert-Butyl-2-chloro-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

生成物 1

HCID 734271375-(7-Tert-butyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine収率 22%

試薬・触媒・溶媒 2

HCID 11714597
Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)
触媒
HCID 6342Acetonitrile溶媒

反応条件

温度
150 °C

実験手順

A microwave vial was charged with 7-tert-butyl-2-chloro-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (50 mg, 0.16 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (70 mg, 0.32 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (11 mg, 0.02 mmol, 10 mol %) then sealed. The vessel was evacuated and back filled with nitrogen before the addition of sodium carbonate (0.25 mL, 0.25 mmol, 1M aqueous solution) and acetonitrile (0.75 mL). The mixture was heated at 150° C. for 30 minutes using microwave irradiation before the mixture was filtered and the filtrate concentrated in vacuo. The resultant residue purified by column chromatography (SiO2, 0-5% methanol in DCM) then triturated with cyclohexane/diethyl ether to give 108 as a white solid (13 mg, 22%). LCMS: RT=4.04 min, [M+H]+=373. 1H NMR (400 MHz, CDCl3): δ 9.14 (2H, s), 5.25 (2H, s), 4.44 (1H, dd, J=11.08, 1.92 Hz), 3.99 (1H, dd, J=8.97, 1.89 Hz), 3.91-3.69 (9H, m), 1.12 (9H, s).

後処理

  1. customthen sealed
  2. customThe vessel was evacuated
  3. custommicrowave irradiation before the mixture
  4. filtrationwas filtered
  5. concentrationthe filtrate concentrated in vacuo
  6. customThe resultant residue purified by column chromatography (SiO2, 0-5% methanol in DCM)
  7. customthen triturated with cyclohexane/diethyl ether

出典と根拠

ORDレコード
ord-bfc32aa4ad9841799593650d03f4b42f
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09346817B2

反応ノート

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