Trifluoroacetic acid → HCID 178492707, 화합물

HRID 2280017

반응식

HRID 2280017 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]3([CH2:15][CH2:14]3)[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:47]=[CH:46][C:26]([C:27]([NH:29][C@H:30]2[CH2:35][CH2:34][C@H:33]([N:36]3[CH2:41][CH2:40][N:39]([CH2:42][CH:43]4[CH2:45][CH2:44]4)[CH2:38][CH2:37]3)[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:48][CH3:49].C(O)(C(F)(F)F)=O>>[CH:16]1([N:7]2[CH2:8][C:9]3([CH2:15][CH2:14]3)[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[CH:47]=[CH:46][C:26]([C:27]([NH:29][C@H:30]5[CH2:31][CH2:32][C@H:33]([N:36]6[CH2:41][CH2:40][N:39]([CH2:42][CH:43]7[CH2:45][CH2:44]7)[CH2:38][CH2:37]6)[CH2:34][CH2:35]5)=[O:28])=[CH:25][C:24]=4[O:48][CH3:49])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

참가 물질

4

반응물 3

HCID 6422Trifluoroacetic acidHCID 579699392-chloro-9-cyclopentyl-8,9-dihydro-5-methylspiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-6(7H)-one3회HCID 178492706HCID 178492706, 화합물2회

생성물 1

HCID 178492707HCID 178492707, 화합물수율 37.2%

실험 절차

2′-Chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepin]-6′(5′H)-one (Intermediate 2) (0.14 g, 0.45 mmol, 1 eq), 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (Intermediate 11) (0.26 g, 0.67 mmol, 1.5 eq) and TFA (0.17 mL, 2.2 mmol, 5 eq) in TFE (3 mL) were heated together at 80° C. for 18 hours. Further quantity of Intermediate 2 (0.14 g) was added and the reaction further heated for 48 hours. RM was concentrated in vacuo and the residue was purified by flash column chromatography on silica eluting with 0→20% ammonia/MeOH in DCM gradient followed by preparative HPLC (Preparative—4) then finally preparative RP-HPLC-MS (Preparative 1) to give 4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-N-((trans)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (0.11 g, 25%).

후처리

  1. customthe reaction
  2. temperaturefurther heated for 48 hours
  3. concentrationRM was concentrated in vacuo
  4. customthe residue was purified by flash column chromatography on silica eluting with 0→20% ammonia/MeOH in DCM gradient

출처 및 근거

ORD 기록
ord-14d63e76d3bf4066bc19d4fe59198888
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133199B2

연결된 노트

불러오는 중…