Diisopropylethylamine → HCID 57955617, 화합물

HRID 914241노트

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HRID 914241 반응식
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:33][CH:34]1[CH2:37][N:36]([CH:38]2[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]2)[CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:33][CH:34]5[CH2:35][N:36]([CH:38]6[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]6)[CH2:37]5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 45072277Tert-butyl 4-(3-aminoazetidin-1-YL)piperidine-1-carboxylate

생성물 1

HCID 57955617HCID 57955617, 화합물수율 14%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid (100 mg, 0.22 mmol) in DMF (1 mL) was added tert-butyl 4-(3-aminoazetidin-1-yl)piperidine-1-carboxylate (72 mg, 0.25 mmol), HATU (125 mg, 0.33 mmol), and DIEA (80 μL, 0.44 mmol). The reaction mixture was stirred for 1 h. It was then poured into 100 mL of rapidly stirring water. A white solid forms and was filtered, washed with water and dried. This solid was treated with TFA in DCM (3 mL 1:1) for 2 days. The solvent was then removed, and the product purified by reverse phase HPLC, free based and lyophilized to yield a white solid (17.8 mg, 14% yield 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (br. s., 2H) 1.50-1.79 (m, 9H) 1.93 (br. s., 2H) 2.07 (br. s., 1H) 2.35-2.44 (m, 2H) 2.85-3.00 (m, 4H) 3.52 (t, J=7.20 Hz, 2H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.37-4.50 (m, 1H) 4.68-4.84 (m, 1H) 7.47-7.52 (m, 2H) 7.98 (s, 1H) 8.26 (s, 1H) 8.29 (d, 1H) 8.61 (d, J=6.57 Hz, 1H). [M+H] calc'd for C29H38F2N8O3, 585. found 585.

후처리

  1. filtrationA white solid forms and was filtered
  2. washwashed with water
  3. customdried
  4. additionThis solid was treated with TFA in DCM (3 mL 1:1) for 2 days
  5. customThe solvent was then removed
  6. customthe product purified by reverse phase HPLC
  7. customto yield a white solid (17.8 mg, 14% yield 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (br. s., 2H) 1.50-1.79 (m, 9H) 1.93 (br. s., 2H) 2.07 (br. s., 1H) 2.35-2.44 (m, 2H) 2.85-3.00 (m, 4H) 3.52 (t, J=7.20 Hz, 2H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.37-4.50 (m, 1H) 4.68-4.84 (m, 1H) 7.47-7.52 (m, 2H) 7.98 (s, 1H) 8.26 (s, 1H) 8.29 (d, 1H) 8.61 (d, J=6.57 Hz, 1H)

출처 및 근거

ORD 기록
ord-d27ab7336032476ba6b4ebd5c9029ce6
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026234B2

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