(R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal → N-(5-((R)-((R)-3-(tert-Butyldimethylsilyloxy)pyrrolidin-1-yl)(4-chloro-2-fluorophenyl)methyl)thiazol-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 2043235Notes

Reaction equation

HRID 2043235 reaction equation
[Si:1]([O:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C@@H:14]([C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=2[F:44])[C:15]2[S:19][C:18]([NH:20][C:21]([C:23]3([C:26]4[CH:36]=[CH:35][C:29]5[O:30][C:31]([F:34])([F:33])[O:32][C:28]=5[CH:27]=4)[CH2:25][CH2:24]3)=[O:22])=[N:17][CH:16]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O1C2C=CC(C3(C(NC4SC([C@@H](N5CC[C@@H](O[Si](C(C)(C)C)(C)C)C5)C5C=CC(F)=CC=5Cl)=CN=4)=O)CC3)=CC=2OC1.N[C@@H](C1C=CC(Cl)=CC=1F)C1SC(NC(C2(C3C=CC4OC(F)(F)OC=4C=3)CC2)=O)=NC=1.[Si](O[C@@H](CCl)CC=O)(C(C)(C)C)(C)C>CC#N>[Si:1]([O:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C@H:14]([C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=2[F:44])[C:15]2[S:19][C:18]([NH:20][C:21]([C:23]3([C:26]4[CH:36]=[CH:35][C:29]5[O:30][C:31]([F:34])([F:33])[O:32][C:28]=5[CH:27]=4)[CH2:24][CH2:25]3)=[O:22])=[N:17][CH:16]=2)[CH2:10]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 13963153(R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanalHCID 59757100(S)-N-(5-(amino(4-chloro-2-fluorophenyl)methyl)thiazol-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamideHCID 59757120N-(5-((S)-((R)-3-(tert-Butyldimethylsilyloxy)pyrrolidin-1-yl)(4-chloro-2-fluorophenyl)methyl)thiazol-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamideHCID 597571341-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide

Product 1

HCID 86660891N-(5-((R)-((R)-3-(tert-Butyldimethylsilyloxy)pyrrolidin-1-yl)(4-chloro-2-fluorophenyl)methyl)thiazol-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-(5-((S)—((R)-3-(tert-Butyldimethylsilyloxy)pyrrolidin-1-yl)(4-chloro-2-fluorophenyl)methyl)thiazol-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide was made by the procedure used for 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((S)—((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide, starting from (S)—N-(5-(amino(4-chloro-2-fluorophenyl)methyl)thiazol-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide and (R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal (90%). 1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 7.63 (t, J=8.2 Hz, 1H), 7.43-7.32 (m, 5H), 7.20 (dd, J=1.5, 8.3 Hz, 1H), 4.93 (s, 1H), 4.39-4.34 (m, 1H), 2.69 (dd, J=6.1, 9.8 Hz, 1H), 2.49-2.45 (m, 2H), 2.34 (dd, J=3.9, 9.9 Hz, 1H), 2.10-1.99 (m, 1H), 1.62-1.55 (m, 1H), 1.52-1.49 (m, 2H), 1.24-1.19 (m, 2H), 0.83 (s, 9H), 0.01 (s, 3H), −0.01 (s, 3H); HPLC ret. time 3.79 min, 10-99% CH3CN, 5 min run; ESI-MS 666.3 m/z (MH+).

Sources & evidence

ORD record
ord-cf6ac57508a64e0eb1b1f0d51efce3a7
Source dataset
uspto-grants-2013_11
Patent number
US08586615B2

Reaction notes

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