Methyl bromoacetate → HCID 178501623, 화합물

HRID 1943487노트

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HRID 1943487 반응식
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:28](CC3C=CC(OC)=CC=3)[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[CH:23][C:22]=4[F:27])=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Br[CH2:54][C:55]([O:57][CH3:58])=[O:56]>C(Cl)Cl>[F:27][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:21]=1[NH:20][C:18]([C:15]1[N:13]2[N:14]=[C:9]([NH:8][C@H:5]3[CH2:6][CH2:7][C@H:2]([NH:1][CH2:54][C:55]([O:57][CH3:58])=[O:56])[CH2:3][CH2:4]3)[CH:10]=[C:11]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:12]2=[N:17][CH:16]=1)=[O:19]

참가 물질

5

반응물 3

HCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 178490937HCID 178490937, 화합물

생성물 1

HCID 178501623HCID 178501623, 화합물수율 52.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
50 °C

실험 절차

To a solution of 5C (40 mg, 0.057 mmol) in CH2Cl2 (1 mL) was added DIEA (0.043 mL, 0.248 mmol) and methyl 2-bromoacetate (9.68 mg, 0.063 mmol). The solution was heated to 50° C. overnight. The volatiles were removed via a stream of nitrogen. The resulting dark brown oil was taken up in TFA (0.75 mL) and heated to 65° C. for 2 h, and then cooled to room temperature. The volatiles were removed under a stream of nitrogen and the crude material was diluted with 1 mL of THF and purified via preparatory HPLC using a YMC ODS C-18 30×250 mm column with 10-100% B (Solvent A: 10% aq MeOH with 0.1% TFA; Solvent B: 90% aq. MeOH with 0.1% TFA) and a linear gradient over 60 min at 25 mL/min, monitoring at 220 nm, and a total run time of 70 min. (Rt of desired=46.365 min) Appropriate fractions were concentrated and lyophilized overnight to afford methyl N-(trans-4-((3-((3-fluoro-4-pyridinyl)carbamoyl)-8-(2-pyridinylamino)imidazo[1,2-b]pyridazin-6-yl)amino)cyclohexyl)glycinate (23 mg, 0.030 mmol, 52.5% yield). HPLC Rt=3.335 minutes. (Phenomenex Luna 5 micron C18 4.6×30 mm: 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA. [M+H]=534.1.

후처리

  1. customThe volatiles were removed via a stream of nitrogen
  2. temperatureheated to 65° C. for 2 h
  3. temperaturecooled to room temperature
  4. customThe volatiles were removed under a stream of nitrogen
  5. additionthe crude material was diluted with 1 mL of THF
  6. custompurified via preparatory HPLC
  7. concentrationa total run time of 70 min. (Rt of desired=46.365 min) Appropriate fractions were concentrated
  8. waitlyophilized overnight

출처 및 근거

ORD 기록
ord-7da3481bedc54992b49b67b627249103
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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