Diisopropylethylamine → HCID 71479644, compound

HRID 1907407Notes

Reaction equation

HRID 1907407 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@:8]23[O:16][CH2:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17]C(=O)OC(C)(C)C)=[N:9]3)[CH:7]=1.[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([C:33](O)=[O:34])=[N:31][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:17][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:14][CH2:15][O:16][C@:8]2([C:6]2[CH:7]=[C:2]([NH:1][C:33](=[O:34])[C:30]3[CH:29]=[CH:28][C:27]([Cl:26])=[CH:32][N:31]=3)[CH:3]=[CH:4][C:5]=2[F:25])[N:9]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27628725-Chloro-2-picolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86762143HCID 86762143, compound

Product 1

HCID 71479644HCID 71479644, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (±)-tert-butyl (4aR,7aR)-7a-(5-amino-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate from step G of Preparation 1 (9 mg), 5-chloropicolinic acid (7 mg), HATU (14 mg), and DIEA (11 μL), in DMF (0.12 mL) was stirred at rt for 2 h, and the crude reaction mixture was subjected to preparative HPLC eluting with 0-100% B (A: 95% H2O/5% MeCN, 10 mM NH4OAc; B: 5% H2O/95% MeCN, 10 mM NH4OAC over 12 min period to give the title compound as a white foam (6 mg, 48%). 1H NMR (500 MHz, CDCl3) δ 9.87 (1H, s), 8.60 (1H, s), 8.26 (1H, d, J=8.5 Hz), 8.02 (1H, br d), 7.92 (1H, dd, J=2.0, 8.0 Hz), 7.72 (1H, m), 7.14 (1H, t, J=10.5 Hz), 4.20 (2H, m), 3.32 (1H, m), 3.02 (1H, m), 2.90 (1H, m), 2.40 (1H, m), 2.24 (1H, m), and 1.51 (9H, s). MS (M+H)+:505.3.

Workup

  1. customthe crude reaction mixture
  2. washeluting with 0-100% B (A: 95% H2O/5% MeCN, 10 mM NH4OAc

Sources & evidence

ORD record
ord-d57a22d129e245d1bdbea5b60070276e
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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