Triethylamine → HCID 56666620, 화합물

HRID 1687219노트

반응식

HRID 1687219 반응식
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[C:14]([Cl:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]2[CH:31]=[CH:30][C:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][O:28][CH3:29])[CH2:24][CH2:25][C:19]=3[CH:18]=2)[N:10]=1.C(N(CC)CC)C.[F:39][C:40]([F:47])([F:46])[CH2:41][S:42](Cl)(=[O:44])=[O:43]>C(Cl)Cl>[Cl:15][C:14]1[C:9]([NH:8][C@@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]2[NH:1][S:42]([CH2:41][C:40]([F:47])([F:46])[F:39])(=[O:44])=[O:43])=[N:10][C:11]([NH:16][C:17]2[CH:31]=[CH:30][C:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][O:28][CH3:29])[CH2:24][CH2:25][C:19]=3[CH:18]=2)=[N:12][CH:13]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 742422,2,2-Trifluoroethanesulfonyl chlorideHCID 566631734-N-[(1R,2R)-2-aminocyclohexyl]-5-chloro-2-N-[3-(2-methoxyethyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]pyrimidine-2,4-diamine

생성물 1

HCID 56666620HCID 56666620, 화합물수율 53%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

N*4*-((1R,2R)-2-Amino-cyclohexyl)-5-chloro-N*2*-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-pyrimidine-2,4-diamine was dissolved in Methylene chloride (5 mL) and Triethylamine (0.15 mL, 1.1 mmol) was added, followed by 2,2,2-Trifluoroethanesulfonyl chloride (0.025 mL, 0.23 mmol). Stir under an atmosphere of Nitrogen at room temperature for 45 min, then partition between 10 mL satd. sodium bicarbonate and 10 mL DCM. Separate and extract the aqueous layer, 3×10 mL DCM. Dry the combined organics over sodium sulfate, filter and concentrate in vacuo. The resultant oil was purified on a sulfonic acid resin cartridge, washing with methanol, eluting with ammonia/methanol. Conc. in vacuo reconcentrating from DCM afforded an oil. Subsequent purification on silica gel (0-10% MeOH:DCM, 12 g SiO2) gave 2,2,2-Trifluoro-ethanesulfonic acid ((1R,2R)-2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-amide (55 mg, 53%) as a colorless film. LCMS (m/e) 591 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.88 (s, 1H), 7.21 (d, 1H, J=7.9 Hz), 7.18 (s, 1H), 7.01 (d, 1H, J=7.9 Hz), 6.97 (s, 1H), 5.36 (d, 1H, J=7.5 Hz), 5.31 (s, 1H), 3.84 (m, 1H), 3.61 (q, 2H, J=9.0 Hz), 3.55 (t, 2H, J=5.4 Hz), 3.36 (s, 3H), 3.29 (m, 1H), 2.9 (m, 4H), 2.72 (m, 6H), 2.17 (m, 2H), 1.82 (m, 2H), 1.34 (m, 4H).

후처리

  1. custompartition between 10 mL
  2. customSeparate
  3. extractionextract the aqueous layer, 3×10 mL DCM
  4. dry with materialDry the combined organics over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customThe resultant oil was purified on a sulfonic acid resin cartridge
  8. washwashing with methanol
  9. washeluting with ammonia/methanol
  10. customafforded an oil
  11. customSubsequent purification on silica gel (0-10% MeOH:DCM, 12 g SiO2)

출처 및 근거

ORD 기록
ord-e4413209bf7e47d38b9b2e594465634c
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148391B2

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