Diisopropylethylamine → HCID 89907813, 화합물

HRID 525743노트

반응식

HRID 525743 반응식
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[N:15]=[CH:14][C:13]([C:16](=[O:29])[NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)=[CH:12][C:8]=2[C:9]([OH:11])=O)[CH2:3]1.F[P-](F)(F)(F)(F)F.[N:37]1(OC(N(C)C)=[N+](C)C)[C:41]2N=CC=[CH:45][C:40]=2N=N1.CCN(C(C)C)C(C)C.C(N)C#C>CN(C=O)C.CCOC(C)=O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([C:9]([NH:37][CH2:41][C:40]#[CH:45])=[O:11])=[CH:12][C:13]([C:16]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)=[O:29])=[CH:14][N:15]=2)[CH2:3]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 239041PropargylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118044993HCID 118044993, 화합물

생성물 1

HCID 89907813HCID 89907813, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of (R)-2-(3-hydroxypyrrolidin-1-yl)-5-((4-(trifluoromethoxy)phenyl)carbamoyl)nicotinic acid (Stage 72.3, 1.50 g, 3.65 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 1.66 g, 4.38 mmol) and DIPEA (0.566 g, 4.38 mmol) in DMF (40 mL) was stirred at RT for 15 min and then propargylamine (0.35 mL, 5.47 mmol) was added. The mixture was stirred for 3 h and then treated with EtOAc, washed with sat. aq. solution of NaHCO3 and brine. The organic phase was dried over Na2SO4 and the solvent was evaporated off under reduced pressure and the residue was crystallized from TBME/EtOAc to afford the product as a colorless crystalline solid. m.p. 246-248° C., HPLC (Condition 4) tR=4.79 min, UPLC-MS (Condition 8) tR=0.89 min, m/z=449.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.78-2.01 (m, 2H), 3.15 (t, J=2.54 Hz, 1H), 3.24 (d, J=12.12 Hz, 1H), 3.43-3.69 (m, 3H), 4.03 (d, J=4.30 Hz, 2H), 4.33 (br. s, 1H), 4.96 (d, J=3.13 Hz, 1H), 7.34 (d, J=8.99 Hz, 2H), 7.79-7.90 (m, 2H), 8.04 (d, J=2.35 Hz, 1H), 8.75 (d, J=2.35 Hz, 1H), 8.96 (t, J=5.67 Hz, 1H), 10.20 (s, 1H).

후처리

  1. stirringThe mixture was stirred for 3 h
  2. washwashed with sat. aq. solution of NaHCO3 and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customthe solvent was evaporated off under reduced pressure
  5. customthe residue was crystallized from TBME/EtOAc

출처 및 근거

ORD 기록
ord-974ad421380f4eb69773f3b748d1c38e
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340537B2

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