N-methyl-2-pyrrolidone → HCID 20598987, compound

HRID 479254Notes

Reaction equation

HRID 479254 reaction equation
[OH:1][C@H:2]1[C@@H:7]([NH:8][C:9](=[O:50])[C@H:10]([CH2:43]C2C=CC=CC=2)[CH2:11][C@H:12]([OH:42])[CH2:13][N:14]2[CH2:19][CH2:18][N:17]([C:20]([CH3:33])([C:22]3[O:23][C:24](C4C=CC=CN=4)=[CH:25][N:26]=3)[CH3:21])[CH2:16][C@H:15]2[C:34]([NH:36][CH2:37][C:38]([F:41])([F:40])[F:39])=[O:35])[C:6]2[CH:51]=[CH:52][CH:53]=[CH:54][C:5]=2[O:4][CH2:3]1.CC[N:57]([CH:61]([CH3:63])C)[CH:58]([CH3:60])C.[CH:64]1[CH:65]=[CH:66][C:67]2N(O)N=N[C:68]=2[CH:69]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[F:91][P-](F)(F)(F)(F)F.CN1[C:103](=[O:104])[CH2:102][CH2:101]C1>>[F:91][C:68]1[CH:67]=[CH:66][C:65]([C:24]2[O:23][C:22]([C:20]([N:17]3[CH2:18][CH2:19][N:14]([CH2:13][C@@H:12]([OH:42])[CH2:11][C@@H:10]([CH2:43][C:103]4[O:104][C:63]5=[CH:61][N:57]=[CH:58][CH:60]=[C:101]5[CH:102]=4)[C:9]([NH:8][C@H:7]4[C:6]5[CH:51]=[CH:52][CH:53]=[CH:54][C:5]=5[O:4][CH2:3][C@H:2]4[OH:1])=[O:50])[C@H:15]([C:34]([NH:36][CH2:37][C:38]([F:40])([F:41])[F:39])=[O:35])[CH2:16]3)([CH3:21])[CH3:33])=[N:26][CH:25]=2)=[CH:64][CH:69]=1

Participants

6

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10283896HCID 10283896, compound

Product 1

HCID 20598987HCID 20598987, compound

Procedure

This intermediate was prepared in the same manner as that of Example 109 Step A, employing carboxylic-acid from Example 66 Step,D (12.85 g; 26.6 mmol) in dry NMP (10 mL), DIEA (18.5 mL; 106.4 mmol), HOBt (8.09 g; 59.9 mmol), intermediate from Step A above (6.3 g; 33.25 mmol), and HBTU (15.1 g; 39.9 mmol). The residue resulting after workup was purified by flash column chromatography (gradient elution 45% to 50% to 55% EtOAc/hexane) to provide the desired product. 1H NMR (500 MHz, CDCl3): δ1.26 (s, 3H), 1.29 (s, 3H), 2.34 (apparent td, J=3.2, 11.7 Hz, 1H), 2.44 (dd, J=3.9, 11.7 Hz, 1H), 2.85 (d, J=10.9 Hz, 1H), 3.22-3.32 (broad, 1H), 3.66 (d, J=11.9 Hz, 1H), 3.75-4.27 (broad, 3H), 4.50 (apparent dd, J=3.7, 18.8 Hz, 1H), 4.68 (d, J=5.0 Hz, 2H), 4.82 (s, 1H), 4.88 (1/2ABX, J=6.8, 18.7 Hz, 1H), 5.28 (d, J=10.5 Hz, 1H), 5.34 (d, J=16.9 Hz, 1H), 5.90-6.00 (br s, 1H), 6.62-6.72 (br s, 1H), 7.17 (apparent t, J=8.6 Hz, 2H), 8.00 (m, 2H), 8.15-8.25 (br s, 1H); electrospray ionization mass spectrum: m/e 517.3 (MH+ calcd for C23H29F4N4O5, 517.2).

Workup

  1. customThis intermediate was prepared in the same manner as that of Example 109 Step A
  2. customThe residue resulting after workup
  3. customwas purified by flash column chromatography (gradient elution 45% to 50% to 55% EtOAc/hexane)

Sources & evidence

ORD record
ord-79f78e9e7938466f844fe48914c9bf1e
Source dataset
uspto-grants-2003_11
Patent number
US06642237B1

Reaction notes

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