Acetic Acid → 3-{1-[6-(2-cyclopropylmethyl-7-methyl-3H-benzimidazol-5-yloxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

HRID 1846543노트

반응식

HRID 1846543 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([CH:32]=[C:33]([CH3:36])[C:34]=1[NH2:35])[O:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:31])[CH2:14][CH2:13]2)[CH:7]=1.[CH:37]1([CH2:40][C:41](O)=O)[CH2:39][CH2:38]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(=O)C>CN(C=O)C>[CH:37]1([CH2:40][C:41]2[NH:1][C:2]3[CH:3]=[C:4]([O:5][C:6]4[N:11]=[CH:10][N:9]=[C:8]([N:12]5[CH2:13][CH2:14][CH:15]([N:18]6[CH2:24][CH2:23][C:22]7[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=7[NH:20][C:19]6=[O:31])[CH2:16][CH2:17]5)[CH:7]=4)[CH:32]=[C:33]([CH3:36])[C:34]=3[N:35]=2)[CH2:39][CH2:38]1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 138440Cyclopropaneacetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669783753-{1-[6-(3,4-Diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

생성물 1

HCID 462446763-{1-[6-(2-cyclopropylmethyl-7-methyl-3H-benzimidazol-5-yloxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

0.20 g (0.42 mmol) 3-{1-[6-(3,4-diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, 46 mg (0.46 mmol) cyclopropyl-acetic acid, 151 mg (0.47 mmol) TBTU and 0.14 mL (1.00 mmol) TEA in 2.00 mL DMF were stirred for 4 h at RT. Then 2.00 mL glacial acetic acid was added and the mixture was stirred overnight at RT. In addition the reaction mixture was stirred for 1 h at 100° C., then cooled and purified by preparative HPLC-MS. The product-containing fractions were combined and the acetonitrile was evaporated down. The residue was made alkaline with 4N aqueous sodium hydroxide solution, the precipitate formed was suction filtered, washed with water and dried under HV.

후처리

  1. additionIn addition the reaction mixture
  2. stirringwas stirred for 1 h at 100° C.
  3. temperaturecooled
  4. custompurified by preparative HPLC-MS
  5. customthe acetonitrile was evaporated down
  6. customthe precipitate formed
  7. filtrationfiltered
  8. washwashed with water
  9. customdried under HV

출처 및 근거

ORD 기록
ord-cbba410d95704ec09917d0c24ee01f0d
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952014B2

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