Potassium Phosphate, Tribasic → 6-(4-(Aminomethyl)phenyl)-1-(cyclohexylmethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 388106노트

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HRID 388106 반응식
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:17]4[CH:31]=[CH:30][C:20]([CH2:21][NH:22]C(=O)OC(C)(C)C)=[CH:19][CH:18]=4)[N:15]=3)[NH:10][C:9]2=[O:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.BrC1N=C2N(CC3CCCCC3)C(=O)NC2=NC=1.C(NCC1C=CC(B(O)O)=CC=1)(OC(C)(C)C)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:22][CH2:21][C:20]1[CH:19]=[CH:18][C:17]([C:14]2[N:15]=[C:16]3[N:8]([CH2:7][CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)[C:9](=[O:32])[NH:10][C:11]3=[N:12][CH:13]=2)=[CH:31][CH:30]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 38631634-(tert-Butoxycarbonylaminomethyl)phenylboronic acidHCID 866263916-Bromo-1-(cyclohexylmethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 86626393tert-Butyl 4-(3-(cyclohexylmethyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzylcarbamate

생성물 1

HCID 573943616-(4-(Aminomethyl)phenyl)-1-(cyclohexylmethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

tert-Butyl 4-(3-(cyclohexylmethyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzylcarbamate. 6-Bromo-1-(cyclohexylmethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 55.B) (200 mg, 0.64 mmol), [4-(N-boc-aminomethyl)phenyl]boronic acid (195 mg, 0.77 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (53 mg, 0.06 mmol) and potassium phosphate (550 mg, 2.58 mmol) in DMF (15 mL) and water (1 mL) were reacted according to General Procedure B. The product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated to approximately one third the original volume and treated with potassium carbonate (1.75 M). The desired product was collected by vacuum filtration, washed with water and dried under high vacuum to provide the title compound. The product was used directly in the next step without further purification or characterization. MS (ESI) m/z 438.1 [M+1]+.

후처리

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  2. concentrationThe desired fractions were concentrated to approximately one third the original volume
  3. additiontreated with potassium carbonate (1.75 M)
  4. filtrationThe desired product was collected by vacuum filtration
  5. washwashed with water
  6. customdried under high vacuum

출처 및 근거

ORD 기록
ord-456391c80e8f4601800dd37e42a972cf
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372976B2

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