Diisopropylethylamine → HCID 178492713、化合物

HRID 1676840

反応式

HRID 1676840 の反応式
[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

参加物

6

反応物 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

生成物 2

HCID 178492713HCID 178492713、化合物HCID 178492714HCID 178492714、化合物

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-23ba99b3deb248599a33c9f3fcebe755
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

関連ノート

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