Trifluoroacetic acid → HCID 178492708、化合物

HRID 1044113

反応式

HRID 1044113 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]3([CH2:16][CH2:15][CH2:14]3)[CH2:8][N:7]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:22]=1.[NH2:23][C:24]1[CH:48]=[CH:47][C:27]([C:28]([NH:30][C@H:31]2[CH2:36][CH2:35][C@H:34]([N:37]3[CH2:42][CH2:41][N:40]([CH2:43][CH:44]4[CH2:46][CH2:45]4)[CH2:39][CH2:38]3)[CH2:33][CH2:32]2)=[O:29])=[CH:26][C:25]=1[O:49][CH3:50].C(O)(C(F)(F)F)=O>>[CH:17]1([N:7]2[CH2:8][C:9]3([CH2:16][CH2:15][CH2:14]3)[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:23][C:24]4[CH:48]=[CH:47][C:27]([C:28]([NH:30][C@H:31]5[CH2:32][CH2:33][C@H:34]([N:37]6[CH2:42][CH2:41][N:40]([CH2:43][CH:44]7[CH2:46][CH2:45]7)[CH2:39][CH2:38]6)[CH2:35][CH2:36]5)=[O:29])=[CH:26][C:25]=4[O:49][CH3:50])=[N:22][C:6]2=3)[CH2:21][CH2:20][CH2:19][CH2:18]1

参加物

4

反応物 3

HCID 6422Trifluoroacetic acidHCID 579698622'-Chloro-9'-cyclopentyl-5'-methyl-8',9'-dihydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-one2 回HCID 178492706HCID 178492706、化合物2 回

生成物 1

HCID 178492708HCID 178492708、化合物

実験手順

2′-Chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepin]-6′(5′H)-one (Intermediate 4) (0.065 g, 0.2 mmol, 1 eq), 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (Intermediate 11) (0.24 g, 0.6 mmol, 3 eq) and TFA (75 μL, 1 mmol, 5 eq) in TFE (6 mL) were heated to reflux together 40 hours. RM was concentrated in vacuo and the residue was partitioned between EtOAc and saturated sodium hydrogen carbonate. The organic layer was separated, washed with saturated brine and concentrated in vacuo to a residue that was purified by preparative RP-HPLC-MS (Preparative—1) to give 4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-N-((trans)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide.

後処理

  1. temperatureto reflux together 40 hours
  2. concentrationRM was concentrated in vacuo
  3. customthe residue was partitioned between EtOAc and saturated sodium hydrogen carbonate
  4. customThe organic layer was separated
  5. washwashed with saturated brine
  6. concentrationconcentrated in vacuo to a residue that
  7. customwas purified by preparative RP-HPLC-MS (Preparative—1)

出典と根拠

ORDレコード
ord-36e7f2ec865a4bbb9042243c22b2d8ec
出典データセット
uspto-grants-2013_10
特許番号
US08563542B2

関連ノート

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