Diisopropylethylamine → HCID 89907813, compound

HRID 525743Notes

Reaction equation

HRID 525743 reaction equation
[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

Participants

7

Reactant 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, compound

Product 1

HCID 89907813HCID 89907813, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-974ad421380f4eb69773f3b748d1c38e
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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