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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
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HRID 528480 반응식
[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]
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참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 11714597
Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)
촉매
HCID 6342Acetonitrile용매

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온도
150 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-bfc32aa4ad9841799593650d03f4b42f
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09346817B2

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