Potassium Carbonate → Benzyl 2-(2-(2-(4-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-oxo-3,4-dihydropyrazin-2-ylamino)propan-2-yl)phenoxy)ethyl(methyl)carbamate

HRID 1697437노트

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HRID 1697437 반응식
[CH:1]1([NH:4][C:5](=[O:31])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[OH:29])([CH3:22])[CH3:21])[C:14]3=[O:30])[CH:7]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:39][CH2:40][N:41]([CH3:52])[C:42](=[O:51])[O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C(#N)C>[CH:1]1([NH:4][C:5]([C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[O:29][CH2:39][CH2:40][N:41]([CH3:52])[C:42](=[O:51])[O:43][CH2:44][C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)([CH3:22])[CH3:21])[C:14]3=[O:30])[CH:7]=2)=[O:31])[CH2:3][CH2:2]1

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 13592063Benzyl (2-chloroethyl)methylcarbamateHCID 66686301N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide

생성물 1

HCID 66690281Benzyl 2-(2-(2-(4-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-oxo-3,4-dihydropyrazin-2-ylamino)propan-2-yl)phenoxy)ethyl(methyl)carbamate수율 55.9%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
85 °C

실험 절차

To N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide (Example 134, 4.3 g) in acetonitrile (5 mL) was added potassium carbonate (2.84 g) followed by benzyl 2-chloroethyl(methyl)carbamate (2.69 g) and the reaction heated at 85° C. for 16 h under nitrogen. After cooling to room temperature, the mixture was evaporated to dryness and the residue partitioned between water (20 mL) and DCM (20 mL). The aqueous layer was separated and further extracted into DCM (2×20 mL). The combined organics were evaporated to leave crude benzyl 2-(2-(2-(4-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-oxo-3,4-dihydropyrazin-2-ylamino)propan-2-yl)phenoxy)ethyl(methyl)carbamate (3.50 g) as a gum. Ethanol (150 mL) and P/C (0.611 g of 5%) were added and the reaction stirred under H2 atmosphere (2 bar) for 4 h. The mixture was filtered through Celite (washing pad with aliquots of ethanol) and the combined filtrates evaporated to leave the crude product (2.1 g). Recrystallisation from ethyl acetate gave the title product (1.15 g) as a white solid.

후처리

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was evaporated to dryness
  3. customthe residue partitioned between water (20 mL) and DCM (20 mL)
  4. customThe aqueous layer was separated
  5. extractionfurther extracted into DCM (2×20 mL)
  6. customThe combined organics were evaporated

출처 및 근거

ORD 기록
ord-8f61592d5bf0423dbc360e24c577e0de
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163905B2

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