Dimethylformamide → HCID 86762152, compound

HRID 1907414Notes

Reaction equation

HRID 1907414 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:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:9]3)[CH:7]=1.CN(C(ON1N=N[C:36]2[CH:37]=[CH:38][CH:39]=[N:40][C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN([CH:62]=[O:63])C>>[F:25][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:62](=[O:63])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][N:40]=2)=[CH:7][C:6]=1[C@@:8]12[O:16][CH2:15][CH2:14][C@@H:13]1[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[N:9]2

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 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 86762152HCID 86762152, compoundYield 62.2%

Procedure

A mixture of tert-butyl ((4aR,7aR)-7a-(5-amino-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (step G of Preparation 1, 15 mg, 0.041 mmol), HATU (23.28 mg, 0.061 mmol), and DIEA (14.26 μL, 0.082 mmol) in DMF (136 μL) was stirred at rt for 2 h, and the crude product was purified by prep HPLC (NH4OAc conditions, see Preparation 3) eluting with 0-100% B over 12 min to give tert-butyl ((4aS,7aS)-7a-(2-fluoro-5-(picolinamido)phenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (12 mg, 0.025 mmol, 62.2% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 10.08 (s, 1H), 8.66 (d, J=4.6 Hz, 1H), 8.31 (d, J=7.8 Hz, 1H), 8.06 (dt, J=8.4, 3.6 Hz, 1H), 7.94 (td, J=7.7, 1.7 Hz, 1H), 7.70 (d, J=4.3 Hz, 1H), 7.53 (ddd, J=7.5, 4.8, 1.0 Hz, 1H), 7.13 (dd, J=10.8, 9.0 Hz, 1H), 4.23-4.11 (m, 2H), 3.30 (d, J=12.4 Hz, 1H), 3.00 (br. s., 1H), 2.92-2.86 (m, 1H), 2.39 (dd, J=12.6, 7.4 Hz, 1H), 2.26-2.15 (m, 1H), 2.10 (s, 4H), 2.03 (s, 1H), 1.51 (s, 9H).

Workup

  1. customthe crude product was purified by prep HPLC (NH4OAc conditions, see Preparation 3)
  2. washeluting with 0-100% B over 12 min

Sources & evidence

ORD record
ord-a5e18c3695c746cd955162579aae08d4
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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