3-Hydrazino-6,7-dihydro-5h-benzo[6,7]cyclohepta[1,2-c]pyridazine → (R)-1-(6,7-Dihydro-5H-benzo[6,7]cyclohepta[1,2-C]pyridazin-3-YL)-N3-(7-(pyrrolidin-1-YL)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-YL)-1H-1,2,4-triazole-3,5-diamine

HRID 1918415노트

반응식

HRID 1918415 반응식
[C:1]([N:3]=[C:4](OC1C=CC=CC=1)[NH:5][C:6]1[CH:7]=[CH:8][C:9]2[CH2:15][CH2:14][C@H:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11][C:10]=2[CH:21]=1)#[N:2].[C:29]([N:31]=[C:32](OC1C=CC=CC=1)[NH:33][C:34]1[CH:35]=[CH:36][C:37]2[CH2:43][CH2:42][C@@H:41]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)[CH2:40][CH2:39][C:38]=2[CH:49]=1)#[N:30].[NH:57]([C:59]1[N:64]=[N:63][C:62]2[C:65]3[CH:73]=[CH:72][CH:71]=[CH:70][C:66]=3[CH2:67][CH2:68][CH2:69][C:61]=2[CH:60]=1)[NH2:58]>>[N:63]1[C:62]2[C:65]3[CH:73]=[CH:72][CH:71]=[CH:70][C:66]=3[CH2:67][CH2:68][CH2:69][C:61]=2[CH:60]=[C:59]([N:57]2[C:1]([NH2:2])=[N:3][C:4]([NH:5][C:6]3[CH:7]=[CH:8][C:9]4[CH2:15][CH2:14][C@H:13]([N:16]5[CH2:17][CH2:18][CH2:19][CH2:20]5)[CH2:12][CH2:11][C:10]=4[CH:21]=3)=[N:58]2)[N:64]=1.[N:63]1[C:62]2[C:65]3[CH:73]=[CH:72][CH:71]=[CH:70][C:66]=3[CH2:67][CH2:68][CH2:69][C:61]=2[CH:60]=[C:59]([N:57]2[C:29]([NH2:30])=[N:31][C:32]([NH:33][C:34]3[CH:35]=[CH:36][C:37]4[CH2:43][CH2:42][C@@H:41]([N:44]5[CH2:45][CH2:46][CH2:47][CH2:48]5)[CH2:40][CH2:39][C:38]=4[CH:49]=3)=[N:58]2)[N:64]=1

참가 물질

5

반응물 3

HCID 592955463-Hydrazino-6,7-dihydro-5h-benzo[6,7]cyclohepta[1,2-c]pyridazineHCID 178512232HCID 178512232, 화합물HCID 178512233HCID 178512233, 화합물

생성물 2

HCID 25126770(R)-1-(6,7-Dihydro-5H-benzo[6,7]cyclohepta[1,2-C]pyridazin-3-YL)-N3-(7-(pyrrolidin-1-YL)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-YL)-1H-1,2,4-triazole-3,5-diamineHCID 46215462Bemcentinib

실험 절차

Phenyl (S)—N′-cyano-N-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)carbamimidate and phenyl (R)—N′-cyano-N-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)carbamimidate were treated with 3-hydrazino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazine in a similar manner as described above in Synthetic Example 2 to yield 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(S)-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine and 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(R)-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine. For example, a suspension of a single enantiomer of phenyl N′-cyano-N-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)carbamimidate (0.06 g, 0.16 mmol) and 3-hydrazino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazine (0.036 g, 0.16 mmol) in 1 mL of IPA was stirred at 90° C. for 18 h. After cooling to ambient temperature, the solvent was evaporated and the residue was purified by HPLC to provide enantiomerically pure 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(R)-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine as a yellow solid (0.04 g, 50%). 1H NMR (DMSO-d6, 300 MHz) 9.11 (s, 1H), 7.94 (s, 1H), 7.85 (br s, 2H), 7.72 (m, 1H), 7.46 (m, 3H), 7.37 (m, 2H), 7.06 (m, 1H), 3.46 (m, 4H), 3.12 (m, 2H), 2.72 (m, 4H), 2.61 (m, 3H), 2.25 (m, 5H), 2.09-1.82 (m, 5H) ppm; MS (ES) 507 (M+H).

출처 및 근거

ORD 기록
ord-207adc077e0342e481b7ba206f3cdc5b
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618331B2

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