N-(tert-butoxycarbonyl)glycine → 1,1-dimethylethyl {2-[(2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)amino]-2-oxoethyl}carbamate

HRID 1874828Notes

Reaction equation

HRID 1874828 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]([NH:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([O:29][C:30]3[CH:35]=[C:34]([C:36]#[N:37])[CH:33]=[C:32]([Cl:38])[CH:31]=3)[C:23]=1[F:39])=[O:19])=[CH:12]2.[CH3:40][C:41]([O:44][C:45]([NH:47][CH2:48][C:49](O)=[O:50])=[O:46])([CH3:43])[CH3:42].CCN(C(C)C)C(C)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][NH:20][C:18]([C:13]2[NH:14][C:15]3[C:11]([CH:12]=2)=[CH:10][C:9]([NH:8][C:49](=[O:50])[CH2:48][NH:47][C:45](=[O:46])[O:44][C:41]([CH3:40])([CH3:42])[CH3:43])=[CH:17][CH:16]=3)=[O:19])=[C:23]([F:39])[C:24]=1[O:29][C:30]1[CH:35]=[C:34]([C:36]#[N:37])[CH:33]=[C:32]([Cl:38])[CH:31]=1

Participants

5

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate

Product 1

HCID 866448881,1-dimethylethyl {2-[(2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)amino]-2-oxoethyl}carbamateYield 480.4%

Procedure

5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.060 g, 0.0103 mmol) was treated with N-{[(1,1-dimethylethyl)oxy]carbonyl}glycine (0.018 g, 0.103 mmol), DIPEA (0.090 mL, 0.514 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.079 g, 0.309 mmol) in a similar manner as described herein to afford crude 1,1-dimethylethyl {2-[(2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)amino]-2-oxoethyl}carbamate (0.031 g) as an off-white solid. This material was treated with trifluoroacetic acid (0.30 mL, 3.89 mmol) in dichloromethane (1 mL) for 1 h. The solvent was evaporated to give the title compound (0.011 g, 40%) as a white solid. 1H NMR (400 Hz, DMSO-d6): δ ppm 11.60 (s, 1H), 10.23 (s, 1H), 8.97 (s, 1H), 8.04 (m, 3H), 7.91 (s, 1H), 7.77 (s, 1H), 7.40-7.54 (m, 2H), 7.29-7.40 (m, 2 H), 7.17-7.27 (m, 1H), 7.10 (s, 1H), 4.60 (s, 2H), 3.72 (s, 2H). MS: m/z 526 (M+1).

Sources & evidence

ORD record
ord-7d1934bc3aaf4ab7b76458c91c3e44ea
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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