Diisopropylethylamine → HCID 89907813、化合物

HRID 525743ノート

反応式

HRID 525743 の反応式
[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

参加物

7

反応物 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、化合物

生成物 1

HCID 89907813HCID 89907813、化合物

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-974ad421380f4eb69773f3b748d1c38e
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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