Diisopropylethylamine → HCID 178492713, 화합물

HRID 1676840

반응식

HRID 1676840 반응식
[F:1][C:2]1([F:30])[CH2:8][N:7]([CH:9]([CH3:11])[CH3:10])[C:6]2[N:12]=[C:13]([NH:16][C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=3[O:26][CH3:27])[N:14]=[CH:15][C:5]=2[N:4]([CH3:28])[C:3]1=[O:29].C(N(C(C)C)C(C)C)C.[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([CH:50]3[CH2:55][CH2:54][CH:53]([NH2:56])[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:42][CH2:41]1>CN(C)C=O>[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([C@@H:50]3[CH2:55][CH2:54][C@H:53]([NH:56][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([NH:16][C:13]5[N:14]=[CH:15][C:5]6[N:4]([CH3:28])[C:3](=[O:29])[C:2]([F:30])([F:1])[CH2:8][N:7]([CH:9]([CH3:10])[CH3:11])[C:6]=6[N:12]=5)=[C:18]([O:26][CH3:27])[CH:19]=4)[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:41][CH2:42]1.[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([C@H:50]3[CH2:55][CH2:54][C@H:53]([NH:56][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([NH:16][C:13]5[N:14]=[CH:15][C:5]6[N:4]([CH3:28])[C:3](=[O:29])[C:2]([F:30])([F:1])[CH2:8][N:7]([CH:9]([CH3:10])[CH3:11])[C:6]=6[N:12]=5)=[C:18]([O:26][CH3:27])[CH:19]=4)[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:41][CH2:42]1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 11586738trans-4-(4-(Cyclopropylmethyl)piperazin-1-yl)cyclohexanamineHCID 445467354-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

생성물 2

HCID 178492713HCID 178492713, 화합물HCID 178492714HCID 178492714, 화합물

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 0.08 g (0.19 mmole) of 4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-292), 0.20 mL (1.2 mmole) of ethyldiisopropyl amine and 0.072 mg (0.21 mmole) of a cis/trans mixture of 4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexylamine with trihydrochloride in 2.0 mL of dimethylformamide was added 0.090 g (0.21 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The resulting solid was collected by filtration, washed with saturated sodium carbonate and water, and dried under vacuum. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-70:30) gave 0.024 g of N-[cis-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-301) (Rf: 0.58 in dichloromethane:methanol 7:3) as a white solid and 0.061 g of N-[trans-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-302) (Rf: 0.46 in dichloromethane:methanol 7:3) as a white solid.

후처리

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with saturated sodium carbonate and water
  3. customdried under vacuum
  4. customPurification by silica gel chromatography
  5. washeluting with dichloromethane-methanol (gradient, 100:0-70:30)

출처 및 근거

ORD 기록
ord-23ba99b3deb248599a33c9f3fcebe755
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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