Dichloromethane → (2-{[(4-Aminomethyl-2-hydroxymethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-pyridin-3-yl)-carbamic acid tert-butyl ester

HRID 1592676노트

반응식

HRID 1592676 반응식
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([C:10]#[N:11])[CH:7]=[CH:6][C:5]=1[CH2:12][N:13]([CH2:24][C:25]1[C:30]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:29][CH:28]=[CH:27][N:26]=1)[CH:14]1[C:23]2[N:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:17][CH2:16][CH2:15]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].C(C(C(C([O-])=O)O)O)([O-])=O.C(Cl)Cl>C1COCC1>[C:35]([O:34][C:32](=[O:33])[NH:31][C:30]1[C:25]([CH2:24][N:13]([CH2:12][C:5]2[CH:6]=[CH:7][C:8]([CH2:10][NH2:11])=[CH:9][C:4]=2[CH2:3][OH:2])[CH:14]2[C:23]3[N:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH2:17][CH2:16][CH2:15]2)=[N:26][CH:27]=[CH:28][CH:29]=1)([CH3:38])([CH3:36])[CH3:37]

참가 물질

6

반응물 4

HCID 6344DichloromethaneHCID 38061142,3-DihydroxybutanedioateHCID 21226445Aluminium lithium hydrideHCID 672715862-{[(3-tert-Butoxycarbonylamino-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-5-cyano-benzoic acid methyl ester

생성물 1

HCID 67271682(2-{[(4-Aminomethyl-2-hydroxymethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-pyridin-3-yl)-carbamic acid tert-butyl ester수율 37.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

2-{[(3-tert-Butoxycarbonylamino-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-5-cyano-benzoic acid methyl ester (0.4532 g, 0.86 mmol) was dissolved in dry THF (5 mL) and flushed with Ar. At 0° C., 1.0 M LiAlH4 in THF (8.6 mL, 8.6 mmol) was added dropwise to the solution and was stirred at room temperature for 6 hours. The reaction was cooled to 0° C. and saturated aqueous KNa Tartrate (Rochelle's salt, 10 mL) was added slowly, and then CH2Cl2 (100 mL) was added. The phases were separated and the aqueous phase was extracted with CH2Cl2 (8×75 mL). The organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 0.1620 g (37%) of (2-{[(4-aminomethyl-2-hydroxymethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-pyridin-3-yl)-carbamic acid tert-butyl ester as a yellow solid. 1H NMR (CDCl3) δ 1.54 (s, 9H), 1.62 (s, 6H), 1.97-2.06 (m, 1H), 2.25-2.26 (m, 1H), 2.69-2.82 (m, 2H), 2.95-2.97 (m, 1H), 3.62-3.72 (m, 1H), 3.80 (s, 2H), 3.85-3.99 (m, 3H), 4.22-4.26 (m, 1H), 4.48-4.52 (m, 1H), 7.08-7.23 (m, 4H), 7.39-7.37 (m, 1H), 8.17-8.19 (m, 1H), 8.45-8.51 (m, 1H), 8.65-8.69 (m, 1H), 9.41-9.44 (m, 1H). Deprotection with TFA using General Procedure F gave COMPOUND 406 as a white solid. 1H NMR (CDCl3) δ 1.64-1.68 (m, 4H), 2.02-2.13 (m, 2H), 2.17-2.26 (m, 1H), 2.64-2.69 (m, 1H), 2.77-2.88 (m, 1H), 3.61-3.69 (m, 3H), 3.82-3.88 (m, 3H), 4.06 (d, 1H, J=12.9 Hz), 4.18 (d, 1H, J=11.1 Hz), 4.58 (d, 1H, J=11.4 Hz), 4.92 (s, 2H), 6.93-6.96 (m, 1H), 6.99-7.04 (m, 1H), 7.06-7.10 (m, 1H), 7.13-7.16 (m, 1H), 7.22-7.29 (m, 2H), 7.37 (d, 1H, J=7.5 Hz), 7.91 (d, 1H, J=3.9 Hz), 8.35 (d, 1H, J=3.9 Hz). 13C NMR (CDCl3) δ 19.54, 21.88, 29.55, 46.47, 54.64, 55.47, 58.18, 63.17, 122.36, 122.63, 124.08, 126.62, 130.67, 131.64, 135.21, 135.32, 137.99, 138.29, 142.08, 142.92, 143.78, 143.88, 146.91, 157.29. ES-MS m/z 404 (M+H). Anal. Calcd. for C24H29N5O.0.8H2O.0.1CH2Cl2: C, 67.88; H, 7.28; N, 16.42. Found: C, 67.85; H, 7.3; N, 16.27.

후처리

  1. customflushed with Ar
  2. temperatureThe reaction was cooled to 0° C.
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2 (8×75 mL)
  5. dry with materialThe organic extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

출처 및 근거

ORD 기록
ord-ad2ed5f123f6485aa5e13fd28571100f
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07291631B2

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