Diisopropylethylamine → N-[2-(3,5-difluorophenyl)-1-[5-(o-tolyl)thiazol-4-yl]ethyl]-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]acetamide

HRID 1506637Notes

Reaction equation

HRID 1506637 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]([F:41])([F:40])[C:27]1[C:35]2[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=2[N:29]([CH2:36][C:37]([OH:39])=O)[N:28]=1.CCN(C(C)C)C(C)C.[F:51][C:52]1[CH:53]=[C:54]([CH2:59][CH:60]([C:62]2[N:63]=[CH:64][S:65][C:66]=2[C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][C:68]=2[CH3:73])[NH2:61])[CH:55]=[C:56]([F:58])[CH:57]=1>CN(C=O)C>[F:51][C:52]1[CH:53]=[C:54]([CH2:59][CH:60]([NH:61][C:37](=[O:39])[CH2:36][N:29]2[C:30]3[CH2:31][CH2:32][CH2:33][CH2:34][C:35]=3[C:27]([C:26]([F:25])([F:41])[F:40])=[N:28]2)[C:62]2[N:63]=[CH:64][S:65][C:66]=2[C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][C:68]=2[CH3:73])[CH:55]=[C:56]([F:58])[CH:57]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 788039[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 902803772-(3,5-Difluorophenyl)-1-(5-(o-tolyl)thiazol-4-yl)ethanamine

Product 1

HCID 90281402N-[2-(3,5-difluorophenyl)-1-[5-(o-tolyl)thiazol-4-yl]ethyl]-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

HATU (40 mg, 0.105 mmol) was added to a solution of 2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetic acid (25.0 mg, 0.1 mmol) and DIPEA (0.02 mL, 0.12 mmol) in DMF (0.3 mL). After 10 minutes, 13D (33.1 mg, 0.1 mmol) in 0.2 mL of DMF was added to the reaction. The reaction was stirred for 2 hours. LC/MS shows desired product with a small amount of acid. Purified reaction mixture on prep reverse phase HPLC using 20-80% B over 20 min. (A=0.1% TFA/H2O; B=0.1% TFA/Acetonitrile). Combined pure fractions as determined by LC/MS and lyophilized to provide the desired product. 1H NMR (400 MHz, DMSO) δ 9.23 (s, 1H), 8.89 (d, J=8.3 Hz, 1H), 7.35-7.16 (m, 2H), 7.11 (t, J=7.6 Hz, 1H), 6.99 (t, J=9.5 Hz, 1H), 6.79 (d, J=7.2 Hz, 1H), 6.51 (d, J=6.4 Hz, 2H), 4.83-4.77 (m, 1H), 4.72 (s, 2H), 3.05 (d, J=7.7 Hz, 2H), 2.46-2.21 (m, 4H), 1.87 (s, 3H), 1.61 (s, 4H). MS (m/z) 561 [M+H]+.

Sources & evidence

ORD record
ord-6523951282e2414b9942636a727120fc
Source dataset
uspto-grants-2015_12
Patent number
US09220710B2

Reaction notes

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