3,6-Dibromothieno(3,2-b)thiophene → ((S)-1-((S)-2-(5-{4-[6-{4-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-thieno[3,2-b]thiophen-3-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 716541Notes

Reaction equation

HRID 716541 reaction equation
Br[C:2]1[C:3]2[S:9][CH:8]=[C:7](Br)[C:4]=2[S:5][CH:6]=1.[CH3:11][O:12][C:13](=[O:46])[NH:14][C@H:15]([C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@H:22]1[C:26]1[NH:27][C:28]([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)=[CH:29][N:30]=1)=[O:20])[CH:16]([CH3:18])[CH3:17]>>[CH3:11][O:12][C:13](=[O:46])[NH:14][C@H:15]([C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@H:22]1[C:26]1[NH:27][C:28]([C:31]2[CH:32]=[CH:33][C:34]([C:2]3[C:3]4[S:9][CH:8]=[C:7]([C:34]5[CH:35]=[CH:36][C:31]([C:28]6[NH:27][C:26]([C@@H:22]7[CH2:23][CH2:24][CH2:25][N:21]7[C:19](=[O:20])[C@@H:15]([NH:14][C:13]([O:12][CH3:11])=[O:46])[CH:16]([CH3:17])[CH3:18])=[N:30][CH:29]=6)=[CH:32][CH:33]=5)[C:4]=4[S:5][CH:6]=3)=[CH:35][CH:36]=2)=[CH:29][N:30]=1)=[O:20])[CH:16]([CH3:18])[CH3:17]

Participants

3

Reactant 2

HCID 106139793,6-Dibromothieno(3,2-b)thiopheneHCID 57462153Methyl ((S)-3-methyl-1-oxo-1-((S)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-yl)carbamate

Product 1

HCID 58310447((S)-1-((S)-2-(5-{4-[6-{4-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-thieno[3,2-b]thiophen-3-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl esterYield 28%

Procedure

Compound A26 was synthesized from 3,6-dibromothieno[3,2,b]thiophene (0.335 mmol) and compound 8 (0.738 mmol), following the procedure as described for compound A155. The residue was purified by semi-preparative HPLC to give compound A86 as a yellow solid in 28% yield. 1H NMR (CD3OD, 400 MHz) δ (ppm) 0.92 (d, J=6.69 Hz, 6H), 0.97 (d, J=6.69 Hz, 6H), 1.01 (d, J=6.69 Hz, 2H), 2.01-2.13 (m, 4H), 2.20-2.40 (m, 6H), 3.67 (s, 6H), 3.87-3.93 (m, 2H), 3.99-4.04 (m, 2H), 4.25 (d, J=7.42 Hz, 2H), 5.18-5.21 (m, 2H), 7.37 (s, 2H), 7.79-7.86 (m, 10H); MS (ESI, EI+) m/z=877.5 (MH+).

Workup

  1. customThe residue was purified by semi-preparative HPLC
  2. customto give compound A86 as a yellow solid in 28% yield

Sources & evidence

ORD record
ord-4731f38b78b24e80b1343fedacb2f445
Source dataset
uspto-grants-2015_11
Patent number
US09187496B2

Reaction notes

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